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Updated: Aug 6, 2026
Endotoxin Activity Assay for the Detection of Whole Blood Endotoxemia in Critically Ill Patients
Published on: June 24, 2019
Endotoxin Activity Assay-guided Polymyxin B Hemoperfusion: From Failed Trials to Biological Enrichment
Abstract:
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.
Insights
Polymyxin B hemoperfusion (PMX-HP) shows promise for endotoxic septic shock patients. The TIGRIS trial suggests PMX-HP may reduce mortality in a carefully selected group, warranting further investigation.
Area of Science:
- Critical care medicine
- Immunology
- Biomarker research
Background:
- Septic shock is a major cause of death despite critical care advancements.
- Polymyxin B hemoperfusion (PMX-HP) aims to improve outcomes by removing endotoxin, but trial results are inconsistent.
- Previous trials like EUPHAS, ABDO-MIX, and EUPHRATES showed varied outcomes, suggesting limitations in non-enriched designs.
Purpose of the Study:
- To critically appraise the rationale and limitations of endotoxin activity assay (EAA)-guided PMX-HP.
- To evaluate the latest evidence from the TIGRIS trial on PMX-HP efficacy in endotoxic septic shock.
- To explore the potential of biologically enriched strategies in sepsis treatment.
Main Methods:
- Analysis of data from the TIGRIS trial, a randomized controlled trial.
- Focus on patients with endotoxic septic shock, defined by EAA levels (0.60-0.89) and high organ dysfunction.
- Critical appraisal of EAA assay performance, feasibility, and generalizability.
Main Results:
- In endotoxic septic shock patients (EAA 0.60-0.89, high organ dysfunction), PMX-HP demonstrated a high posterior probability of mortality reduction.
- The mortality reduction was particularly notable at the 90-day follow-up.
- Findings support the concept of a biologically enriched patient selection strategy for PMX-HP.
Conclusions:
- EAA-guided PMX-HP shows potential for treating specific septic shock populations.
- Uncertainties regarding EAA assay performance, feasibility, and generalizability persist.
- Integrating EAA with other biomarkers and clinical phenotypes is crucial for advancing precision medicine in sepsis.
