Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review

Introduction Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer membrane of gram-negative bacteria, is considered important to their pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers ( PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption, theoretically preventing the progression of the biological cascade of sepsis. We performed a systematic review to describe the effect in septic patients of direct hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs, oxygenation, and mortality reported in published studies. Methods We searched PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Prospective and retrospective observational studies, pre- and post-intervention design, and randomized controlled trials were included. Three authors reviewed all citations. We identified a total of 28 publications - 9 randomized controlled trials, 7 non-randomized parallel studies, and 12 pre-post design studies - that reported at least one of the specified outcome measures ( pooled sample size, 1,425 patients: 978 PMX-F and 447 conventional medical therapy). Results Overall, mean arterial pressure ( MAP) increased by 19 mm Hg ( 95% confidence interval [ CI], 15 to 22 mm Hg; p < 0.001), representing a 26% mean increase in MAP ( range, 14% to 42%), whereas dopamine/dobutamine dose decreased by 1.8 mu g/kg per minute ( 95% CI, 0.4 to 3.3 mu g/kg per minute; p = 0.01) after PMX-F. There was significant intertrial heterogeneity for these outcomes ( p < 0.001), which became non-significant when analysis was stratified for baseline MAP. The mean arterial partial pressure of oxygen/fraction of inspired oxygen ( PaO2/FiO(2)) ratio increased by 32 units ( 95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was associated with significantly lower mortality risk ( risk ratio, 0.53; 95% CI, 0.43 to 0.65). The trials assessed had suboptimal method quality. Conclusion Based on this critical review of the published literature, direct hemoperfusion with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO(2) ratio, and mortality. However, publication bias and lack of blinding need to be considered. These findings support the need for further rigorous study of this therapy.