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Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial
Dinna N Cruz1, Massimo Antonelli, Roberto Fumagalli
1Department of Nephrology, Dialysis, and Transplantation, St Bortolo Hospital and International Renal Research Institute Vicenza, 36100 Vicenza, Italy.
Insights
Polymyxin B hemoperfusion improved hemodynamics and organ function in patients with abdominal sepsis. This treatment reduced 28-day mortality compared to conventional therapy alone.
Area of Science:
- Critical Care Medicine
- Nephrology
- Infectious Diseases
Background:
- Sepsis, particularly Gram-negative-induced abdominal sepsis, is associated with high endotoxin levels.
- Polymyxin B fiber column is a medical device designed to reduce blood endotoxin levels.
- Reducing endotoxin levels may improve clinical outcomes in sepsis patients.
Purpose of the Study:
- To evaluate the efficacy of polymyxin B hemoperfusion in addition to conventional therapy for severe sepsis.
- To determine its impact on hemodynamic parameters, oxygenation, organ dysfunction, and mortality.
Main Methods:
- A prospective, multicenter randomized controlled trial (EUPHAS) involving 64 patients with severe sepsis or septic shock from intra-abdominal infections.
- Patients received either conventional therapy or conventional therapy plus two sessions of polymyxin B hemoperfusion.
- Outcomes included changes in mean arterial pressure (MAP), vasopressor requirement, oxygenation (PaO2/FiO2), Sequential Organ Failure Assessment (SOFA) scores, and 28-day mortality.
Main Results:
- The polymyxin B group showed significant improvements in MAP and decreased vasopressor requirements compared to the control group.
- Oxygenation (PaO2/FiO2) and SOFA scores improved in the polymyxin B group, indicating better organ function.
- Twenty-eight-day mortality was significantly lower in the polymyxin B group (32%) compared to the conventional therapy group (53%).
Conclusions:
- Polymyxin B hemoperfusion, when added to conventional therapy, significantly improved hemodynamic status and organ dysfunction in patients with severe sepsis.
- This intervention demonstrated a notable reduction in 28-day mortality in patients with Gram-negative abdominal infections.
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.
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