CONTEXT: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PATIENTS: 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. INTERVENTION: Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34). MAIN OUTCOME MEASURES: 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. RESULTS: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 mmHg; 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). CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00629382.
RCT Entities:
CONTEXT: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PATIENTS: 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. INTERVENTION: Patients were randomized to either conventional therapy (n=30) or conventional therapy plus 2 sessions of polymyxin B hemoperfusion (n=34). MAIN OUTCOME MEASURES: 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. RESULTS: 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). CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00629382.
Authors: M Bernhard; G Marx; K Weismüller; C Lichtenstern; K Mayer; F M Brunkhorst; M A Weigand Journal: Anaesthesist Date: 2010-05 Impact factor: 1.041