Endotoxin: A Bona Fide Treatable Sepsis Endotype?

BACKGROUND: The recognition of syndromes has been a pillar of medical education and knowledge. However, treatment of syndromes is challenging because there is a disconnect between the underlying mechanisms that lead to organ injury and the clinical expression of this injury. This is an important barrier to identifying effective treatments in sepsis which may be resolved by the identification of sepsis endotypes.

SUMMARY: In this review, we discuss the rationale for considering endotoxic septic shock as a true endotype; the mechanisms by which endotoxin induce cell and organ injury and dysfunction, the strategies to recognize when it occurs and the potential treatments, focusing on endotoxin removal through extracorporeal blood purification.

KEY MESSAGES: There is sufficient preclinical and clinical evidence to support the notion that endotoxin is a relevant mechanism of injury in human sepsis that drives poor patient outcomes that can be identified using clinical criteria and biomarkers and that may respond to specific targeted therapies, strongly suggesting that endotoxemic septic shock is a bona fide endotype.