Polymyxin-B hemoperfusion and endotoxin removal: lessons from a review of the literature

Abstract

Sepsis involves a complex interaction between bacterial toxins and the host immune system. Endotoxin, a component of the outer membrane of Gram-negative bacteria, is involved in the pathogenesis of sepsis producing proinflammatory cytokines and activating the complement system, and is thus an ideal potential therapeutic target. Direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-F) has been shown to bind and neutralize endotoxin in both in vitro and in vivo studies. Therefore, this extracorporeal therapy with PMX-F can potentially interrupt the biological cascade of sepsis. A systematic review of the published literature found positive effects of PMX-F on blood pressure and dopamine/dobutamine use, the PaO(2)/FiO(2) ratio, endotoxin removal, and mortality. It should be noted, however, that many of the analyzed studies were of suboptimal quality, which may then exaggerate the magnitude of these effects. Since this meta-analysis, other studies have been published including a multicenter randomized controlled trial on abdominal septic shock. In this study, PMX-F, when added to conventional therapy, significantly improved hemodynamics and organ dysfunction, and reduced 28-day mortality in this targeted population. There is clear biological rationale for endotoxin removal in the clinical management of severe sepsis and septic shock. The current literature seems to provide some support for this premise, and provides the basis for further rigorous study.