Polymyxin B hemoperfusion: a mechanistic perspective

• Published in: Critical care (London, England) Vol. 18; no. 3; p. 309
• Main Authors: Ronco, Claudio, Klein, David J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.06.2014; BioMed Central
• Subjects: Adsorption; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Bacteremia - therapy; Care and treatment; Cytokines - metabolism; Development and progression; Endotoxins - blood; Genetic aspects; Health aspects; Hemoperfusion - instrumentation; Hemoperfusion - methods; Humans; Medical research; Medicine, Experimental; Physiological aspects; Polymyxin B - pharmacokinetics; Polymyxin B - therapeutic use; Septic shock; Shock, Septic - therapy; Viewpoint
• ISSN: 1364-8535; 1466-609X; 1364-8535
• DOI: 10.1186/cc13912

Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridge (PMX-DHP) is an established strategy in the treatment of septic shock in Japan and parts of Western Europe. PMX-DHP is currently the subject of a pivotal North American randomized controlled trial (EUPHRATES) in patients with septic shock and confirmed endotoxemia, as measured by the endotoxin activity assay. The major mechanism of action of this therapy is the removal of circulating endotoxin. High affinity binding of circulating endotoxin by the PMX-DHP column may decrease circulating endotoxin levels by up to 90% after two standard treatments. Basic research has shown reductions in circulating cytokine levels and in renal tubular apoptosis. Clinical research has shown that PMX-DHP therapy results in hemodynamic improvements, improvements in oxygenation, renal function, and reductions in mortality. Further research is needed to further define additional patient populations with endotoxemia that may benefit from PMX-DHP therapy as well as to further elucidate dosing, timing, and additional information on mechanisms of action. This review will present the mechanistic rationale for this targeted strategy of endotoxin removal using PMX-DHP in endotoxemic septic patients, highlighting both the specific effects of the therapy and the evidence accumulated so far of clinical improvement following this therapy in terms of recovery of organ function.