Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock. The EUPHAS Randomized Controlled Trial.

Context PolymyxinBfibercolumnisamedicaldevicedesignedtoreduceblooden- dotoxin levels in sepsis. Gram-negative–induced abdominal sepsis is likely associated with high circulating endotoxin. Reducing circulating endotoxin levels with poly- myxin B hemoperfusion could potentially improve patient clinical outcomes. Objective To determine whether polymyxin B hemoperfusion added to conven- tional medical therapy improves clinical outcomes (mean arterial pressure [MAP], va- sopressor requirement, oxygenation, organ dysfunction) and mortality compared with conventional therapy alone. Design,Setting,andPatients Aprospective,multicenter,randomizedcontrolled trial (Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis [EUPHAS]) con- ducted 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). MainOutcomeMeasures PrimaryoutcomewaschangeinMAPandvasopressor requirement, and secondary outcomes were PaO2/FIO2 (fraction of inspired oxygen) ratio, change in organ dysfunction measured using Sequential Organ Failure Assess- ment (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 PaO2/FIO2 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 con- ventional 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. TrialRegistration clinicaltrials.govIdentifier:NCT00629382 JAMA. 2009;301(23):2445-2452