PMX endotoxin removal in the clinical practice: results from the EUPHAS trial

Abstract

Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely to be associated with high circulating endotoxin. In June 2009, the EUPHAS study (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis) was published in JAMA. Sixty-four patients who underwent emergency surgery for intra-abdominal infection between December 2004 and December 2007 were enrolled with severe sepsis or septic shock. Intervention patients were randomized to either conventional therapy (n = 30) or conventional therapy plus two sessions of polymyxin B hemoperfusion (n = 34). The main outcome measures were change in mean arterial pressure (MAP) and vasopressor requirement, and secondary outcomes were the PaO(2)/FiO(2) (fraction of inspired oxygen) ratio, change in organ dysfunction measured using sequential organ failure assessment (SOFA) scores, and 28-day mortality. At 72 h, MAP increased (76 to 84 mm Hg; p = 0.001) and the vasopressor requirement decreased (inotropic score: 29.9 to 6.8; p = 0.001) in the polymyxin B group, but not in the conventional therapy group (MAP: 74 to 77 mm Hg; p = 0.37; inotropic score: 28.6 to 22.4; p = 0.14). The PaO(2)/FiO(2) ratio increased slightly (235 to 264; p = 0.049) in the polymyxin B group, but not in the conventional therapy group (217 to 228; p = 0.79). SOFA scores improved in the polymyxin B group, but not in the conventional therapy group (change in SOFA: -3.4 vs. -0.1; p = 0.001), and 28-day mortality was 32% (11/34 patients) in the polymyxin B group and 53% (16/30 patients) in the conventional therapy group (unadjusted HR: 0.43, 95% CI: 0.20-0.94; adjusted HR: 0.36, 95% CI:0.16-0.80). The study demonstrated how polymyxin B hemoperfusion added to conventional therapy significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality in a targeted population with severe sepsis and/or septic shock from intra-abdominal Gram-negative infections.