Clinical applications for the endotoxin activity assay in sepsis: a scoping review.

BACKGROUND

The Endotoxin Activity Assay™ (EAA) is a commercially available diagnostic test that quantifies endotoxin activity in human whole blood. Despite its promising features, the clinical utility of the EAA in the management of sepsis remains incompletely understood. This study aims to comprehensively review the published literature on the EAA and explore its usage trends and clinical applications in sepsis management.

METHODS

We conducted a scoping review focused on EAA measurement in human sepsis subjects across four major databases: Embase, Web of Science, MEDLINE, and Cochrane Library. All the studies published from the inception of the databases to the search date in May 2025 were screened. Reviews, editorials, conference abstracts, grey literature, and non-human studies were excluded. We extracted and analyzed cohort characteristics, timing and frequency of EAA measurement, and the reported EAA results.

RESULTS

Our systematic search and screening identified 95 articles that applied EAA on human patients, 54 of which focused on sepsis. These studies were published between 2002 and 2025 and reported EAA results in adult and pediatric patients. Most studies were conducted in Europe (51.9%), Asia (22.2%), and North America (11.1%). The most common study scenario involved using EAA as an inclusion criterion for blood purification therapy for sepsis, primarily polymyxin-B hemoadsorption. Of the 54 studies, three were randomized controlled trials conducted in North America, Thailand, and Switzerland. These trials investigated the effect of endotoxin adsorption therapy and continuous renal replacement therapy with adsorption filters for septic shock, using EAA ≥ 0.6 as part of the inclusion criteria. Nearly half of the studies (48.1%) measured EAA levels more than twice per patient, suggesting that serial endotoxin monitoring is of clinical interest.

CONCLUSIONS

Our results highlight the clinical application of EAA measurement in sepsis patient populations worldwide, particularly its potential role in the application of blood purification therapy. Together with other biomarkers and further validation studies to establish relevant timing, frequency, and cut-off values for sepsis patients, the EAA has the potential to become a component of precision medicine in the ICU by identifying patient subgroups most likely to benefit from targeted interventions, such as blood purification.