Endotoxin Activity Assay-guided Polymyxin B Hemoperfusion: From Failed Trials to Biological Enrichment

Septic shock remains a leading cause of mortality despite advances in critical care. Polymyxin B hemoperfusion (PMX-HP) has long been proposed to improve outcomes by removing circulating endotoxin, yet randomized trials have yielded inconsistent results. Early enthusiasm from EUPHAS was followed by neutral findings in ABDO-MIX and EUPHRATES, highlighting the limitations of non-enriched trial designs. The latest evidence from the TIGRIS trial, a randomized controlled trial, provides important new insight. In patients with endotoxic septic shock, defined by an endotoxin activity assay (EAA) of 0.60-0.89 and high organ dysfunction, polymyxin B hemoadsorption was associated with a high posterior probability of mortality reduction, particularly at 90 days. This article critically appraises the rationale and limitations of EAA-guided PMX-HP in light of these updated data. While the findings support a biologically enriched strategy, important uncertainties remain regarding assay performance, feasibility, and generalizability. The integration of EAA with complementary biomarkers and clinical phenotypes is likely necessary to advance precision medicine in sepsis.