Endotoxin Activity Assay-Guided Patient Selection for Polymyxin B Hemoperfusion: Lessons from the TIGRIS Trial and Future Directions

Sepsis and septic shock remain leading global causes of mortality, with endotoxin from Gram-negative bacteria playing a central role in their pathophysiology. Polymyxin B hemoperfusion (PMX-HP) was developed as an adjunctive therapy to directly remove circulating endotoxin in patients with sepsis and septic shock. Early clinical trials yielded conflicting results, largely due to challenges in patient selection. The endotoxin activity assay (EAA) has been investigated as a biomarker to identify patients most likely to benefit, but its limitations include indirect measurement, variability, and poor specificity. The recently completed TIGRIS trial, which enrolled septic shock patients with intermediate EAA values (0.60–0.89) and high organ dysfunction, demonstrated a significant survival benefit, thereby validating a targeted, precision medicine approach. This review critically appraises the role of EAA in guiding PMX-HP, highlights the lessons learned from the TIGRIS trial, and discusses complementary strategies such as integrating additional biomarkers, organ dysfunction scoring, and clinical phenotyping. Future research should embed EAA within multi-dimensional frameworks to optimize patient selection and establish PMX-HP as a precision therapy for endotoxemic sepsis and septic shock.