Extracorporeal endotoxin removal by polymyxin B immobilized fiber cartridge: designing and antiendotoxin efficacy in the clinical application

Abstract

We have developed an extracorporeal hemoadsorption cartridge, the PMX cartridge, to eliminate endotoxin from peripheral blood circulation. As an adsorbent, a polymyxin B covalently immobilized fiber (PMX-F) was developed. After the optimization of the condition of immobilization, fixed polymyxin B maintained its ability to adsorb endotoxin and its bactericidal activity. PMX-F could detoxify many kinds of endotoxin in vitro. Fixed polymyxin B was estimated to interact with the lipid A portion of endotoxin. Utilization of fibrous adsorbents enabled us to design the PMX cartridge with a large surface area and low blood pressure drop in the blood flow compartment and to apply it safely to the direct hemoperfusion procedure. In Japan, the PMX cartridge is now being clinically applied as one of the therapeutical interventions for sepsis, septic shock, and septic multiple organ failure. In multicenter clinical studies, the blood endotoxin level has been significantly decreased. Accompanied with elimination of endotoxin, hemodynamic abnormalities such as low blood pressure and low systemic vascular resistance were significantly improved. In more recent multicenter studies, the average number of failed organs; severity of illness score, such as Goris score; and vasopressor dosage were significantly decreased. The PMX cartridge is expected to be effective in the intervention for the treatment of septic shock. Endotoxin may be one of the therapeutical targets for the treatment of sepsis.