Endotoxin removal: history of a mission

One of the key molecules involved in the pathogenesis of severe sepsis and septic shock is lipopolysaccharide (LPS) or endotoxin, which is a component of the cellular wall of Gram-negative bacteria. Clinical studies have shown that the level of circulating LPS is correlated with illness severity (APACHE II), the onset and amount of organ dysfunction (SOFA) and intensive care unit mortality. Many therapeutic strategies have attempted to neutralize the pathogenic activity of endotoxin in order to interrupt the progression of a septic state towards a worsened clinical framework, i.e. severe sepsis of septic shock. Over the past decades the role of extracorporeal hemoperfusion by means of polymyxin B-based cartridges (PMX-DHP) to bind and neutralize LPS from whole blood has increased in clinical relevance. This is due to an increasing number of studies confirming that a directed therapy of endotoxic shock could significantly influence the course of the septic cascade. This review will outline the meaning of the targeted approach to endotoxin, both highlighting the specific immunologic effect of endotoxin removal by polymyxin B and the evidence of clinical improvements following this kind of therapy in terms of recovery of organ function.