Septic Shock: Death Mechanisms

Abstract

Despite a decrease in early mortality, sepsis is still burden with a poor prognosis related to immunological, cognitive and neuromuscular impairments. The lessons learned from the failures of anti-inflammatory therapies and forty years of translational research have led to a better understanding of its complex pathophysiology: Sepsis is characterized by the simultaneous development of an inflammatory response necessary to eliminate the pathogen but responsible for collateral tissue damages, and an anti-inflammatory response required for healing, but also resulting in a profound and prolonged immunosuppression.

Owing to an earlier management of the infection, situations where patients die early from fulminant inflammation and refractory shock have become quite rare, excepted particular pathogen virulence or genetic susceptibility of the host. In contrast, a majority of patients who survive the early hours of sepsis develop an acquired immune deficiency responsible for nosocomial infections and late mortality up to 75% at five years. Development of targeted therapies aiming at restoring immune capacity of septic patients is the ongoing challenge.