Potential survival benefit and early recovery from organ dysfunction with polymyxin B hemoperfusion: perspectives from a real-world big data analysis and the supporting mechanisms of action

Abstract

Abstract Background Endotoxin (ET) removal therapy with polymyxin B-immobilized fiber column hemoperfusion (PMX-HP) has been used for the treatment of septic shock. Some observational studies reported clinical benefits, particularly in specific subgroups of patients. However, larger randomized controlled trial results have been disappointing. Main body The four studies that revealed the survival benefit of PMX-HP were based on the Japanese Diagnosis Procedure Combination (DPC) national inpatient database (J-DPC study). Nevertheless, one J-DPC study and a randomized controlled trial (RCT) conducted in France evaluated PMX-HP in patients with abdominal septic shock and did not report a significant survival benefit. In both studies, the severity of illness was too low to find substantial significant differences in mortality. The results of the J-DPC studies further suggest that some subpopulations of patients could benefit from PMX-HP. Based on these results, this review revisited prior RCTs and other large-scale studies on PMX-HP. In addition, four J-DPC studies and one large-scale study reported a survival benefit with PMX-HP. A secondary analysis of the EUPHRATES trial, the most recent double-blinded RCT of PMX-HP conducted in North America, suggested a survival benefit in patients with high levels of endotoxemia. In the J-DPC studies and the EUPHRATES trial, ventilator-free days, vasoactive drug-free days, and renal replacement-free days were significantly improved in the PMX-HP groups. These findings suggest that PMX-HP can contribute to early recovery from organ dysfunction. The reduction of supportive care likely provides important health and economic benefits for managing patients with septic shock. Finally, the blood levels of mediators or biomarkers related to respiratory, cardiovascular, and renal dysfunction have been reported to be normalized with PMX-HP. Conclusions These results support the biological rationale for the improvement in organ dysfunction observed in the J-DPC studies and other large-scale studies, including the EUPHRATES trial. Real-world evidence from large data sets suggests an appropriate patient population that are likely to benefit from the utility of PMX-HP for septic shock.