Polymyxin B Hemoperfusion for Sepsis and Septic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND

To evaluate the efficacy and safety of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) therapy in patients with sepsis.

DESIGN

A systematic review and meta-analysis of four major databases: Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, and Science Citation Index Expanded.

STUDY SELECTION

Randomized controlled trials comparing PMX-DHP with conventional therapy on the outcome of mortality in patients with severe sepsis/septic shock.

DATA EXTRACTION

Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. Primary outcomes were mortality and adverse events. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate quality of evidence and grade the strength of recommendation.

RESULTS

In seven trials enrolling 841 patients, assessment for risk of bias indicated variations in study quality from high (n = 4) to unclear (n = 3) resulting from a lack of adequate randomization, blinding, and incomplete outcomes. Polymyxin B-immobilized fiber therapy was associated with lower mortality (risk ratio, 0.65; 95% confidence interval [CI], 0.47-0.89; p = 0.007; I = 72%). Significant heterogeneity among trials was explained partly by study venue and baseline mortality rate. Meta-regression analysis revealed a significant negative slope between effect size of PMX-DHP therapy and baseline mortality rate in individual studies (p = 0.003), suggesting the probability of a beneficial effect with PMX-DHP increased with increasing baseline risk. Polymyxin B-immobilized fiber therapy did not increase the risk of hemoperfusion-related adverse events. The quality of the body of evidence was considered low for both mortality and adverse events.

CONCLUSIONS

Polymyxin B-immobilized fiber therapy was associated with reduced mortality in sepsis/septic shock. Based on the low quality of evidence, therapeutic use of PMX-DHP for survival benefit may be recommended conditionally for patients with high risk of death. Additional large randomized controlled trials are needed to confirm or refute this evidence.