Endotoxin Hemoperfusion as an Adjuvant Therapy for Sepsis: Lessons from the TIGRIS Trial

Abstract

Despite significant advances in antimicrobial therapy and supportive intensive care, mortality in septic shock remains unacceptably high. Hemoadsorption therapies have emerged as adjunctive strategies designed to remove circulating mediators that propagate the dysregulated host response. Among these, polymyxin B hemoperfusion (PMX-HP) represents the most extensively studied extracorporeal modality, specifically targeting circulating endotoxin. Over three decades of investigation have produced a complex body of evidence, ranging from early promising results in small, open-label studies to large randomized trials with inconsistent outcomes. Recent findings from the TIGRIS trial, employing Bayesian design and biomarker-guided patient selection, provide compelling support for a survival benefit in a well-defined subgroup of septic shock patients with intermediate endotoxin activity. This review synthesizes the evolution of PMX-HP research, from EUPHAS through EUPHRATES and TIGRIS, highlighting lessons learned in trial design, biomarker utilization, and patient stratification. These experiences underscore the potential of precision-based extracorporeal interventions in sepsis while outlining the critical methodological and regulatory challenges that remain.