Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock

TLDR

Polymyxin B hemoperfusion is a device that removes endotoxin from the blood, and abdominal gram‑negative sepsis is associated with high endotoxin levels, suggesting that lowering endotoxin could improve outcomes. The study aimed to determine whether adding polymyxin B hemoperfusion to standard therapy improves mean arterial pressure, vasopressor use, oxygenation, organ dysfunction, and mortality in patients with abdominal sepsis. In a prospective, multicenter, randomized controlled trial (EUPHAS) at 10 Italian ICUs, 64 patients with severe sepsis or septic shock were randomized to conventional therapy alone or conventional therapy plus two sessions of polymyxin B hemoperfusion, with primary outcomes of MAP and vasopressor requirement and secondary outcomes of PaO₂/FiO₂, SOFA score, and 28‑day mortality. Polymyxin B hemoperfusion significantly increased MAP, reduced vasopressor requirement, modestly improved PaO₂/FiO₂, lowered SOFA scores, and cut 28‑day mortality from 53 % to 32 % (adjusted HR 0.36).

Abstract

Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels in sepsis. Gram-negative-induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with polymyxin B hemoperfusion could potentially improve patient clinical outcomes.To determine whether polymyxin B hemoperfusion added to conventional medical therapy improves clinical outcomes (mean arterial pressure [MAP], vasopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone.A prospective, multicenter, randomized controlled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) conducted at 10 Italian tertiary care intensive care units between December 2004 and December 2007. Sixty-four patients were enrolled with severe sepsis or septic shock who underwent emergency surgery for intra-abdominal infection.Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34).Primary outcome was change in MAP and vasopressor requirement, and secondary outcomes were 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.MAP increased (76 to 84 mm Hg; P = .001) and vasopressor requirement decreased (inotropic score, 29.9 to 6.8; P < .001) at 72 hours in the polymyxin B group but not in the conventional therapy group (MAP, 74 to 77 mm Hg; P = .37; inotropic score, 28.6 to 22.4; P = .14). The PaO(2)/FIO(2) ratio increased slightly (235 to 264; P = .049) in the polymyxin B group but not in the conventional therapy group (217 to 228; P = .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 < .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 hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20-0.94; adjusted HR, 0.36; 95% CI, 0.16-0.80).In this preliminary study, 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.clinicaltrials.gov Identifier: NCT00629382.