Up-to-date information on polymyxin B-immobilized fiber column direct hemoperfusion for septic shock

Abstract

Endotoxin adsorption therapy by polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) has been used for the treatment of septic shock patients. Endotoxin, an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin triggers a signaling cascade for leukocytes, macrophage, and endothelial cells to secrete various mediators including cytokines and nitric oxide, leading to septic shock and multiple organ dysfunction syndrome. PMX-DHP directly adsorbed not only endotoxin but also monocytes and anandamide. It reduced blood levels of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and IL-17A, adhesion molecules, plasminogen activator inhibitor 1, and high mobility group box-1. As a result, PMX-DHP increased blood pressure and reduced the dose of vasoactive-inotropic agents. PMX-DHP improved monocyte human leukocyte antigen-DR expression in patients with severe sepsis and septic shock. A post hoc analysis of EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in Randomized Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) trial has shown that PMX-DHP significantly reduced 28-day mortality compared with the control group in septic shock patients with endotoxin activity assay level between 0.60 and 0.89. Longer duration of PMX-DHP may be another strategy to bring out the beneficial effects of PMX-DHP. Further studies are needed to confirm the efficacy of PMX-DHP treatment for septic shock.

Keywords: duration of therapy; endotoxin; hemoperfusion; polymyxin B; sepsis; septic shock.

Figure 1.

Recognition of endotoxin (lipopolysaccharide [LPS]) on the surface of phagocytes and mechanism of polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) treatment. LPS is opsonized by LPS-binding protein (LBP), and LPS-LBP complex is recognized by CD14, on the monocyte and macrophage surface. LPS-LBP-CD14 ternary complex activates TLR4, which in turn signals through My88 and interleukin (IL)-1 receptor-associated kinase (IRAK). Signaling pathways activate nuclear factor kappa B (NF-kB), which induces the production of proinflammatory cytokines and nitric oxide (NO). PMX-DHP directly adsorbs endotoxin and reduces circulating level of endotoxin. In addition, PMX-DHP adsorbs monocyte and anandamide. As a result, inflammatory cytokines and NO decrease. TLR4: Toll-like receptor 4; MD2: myeloid differentiation 2; MyD88: myeloid differentiation factor 88; TNF: tumor necrosis factor.