Endotoxin removal: how far from the evidence? From EUPHAS to EUPHRATES

There is a large amount of support for the safety of polymyxin-B (PMX-B) hemoperfusion in the treatment of septic shock from Japan and Europe. There is also support for potential efficacy, although randomized controlled trials are few and conflicting. PMX-B hemoperfusion represents a promising new treatment that could significantly improve survival. Previous clinical trials of PMX-B have been criticized for methodological issues, such as the absence of blinding, the use of surrogate outcomes and lack of longer term mortality outcomes. The variability in the number of treatment cartridges used, the selection of subjects based on likelihood of endotoxin presence without endotoxin measurement, and small sample sizes in mainly single-center trials have also been cited. The newly designed EUPHRATES trial (Evaluating Use of Polymyxin Hemoperfusion in a Randomized Controlled Trial of Adults treated for Endotoxemia and Septic Shock) addresses many of the methodological issues and represents a significant opportunity to test for clinical efficacy of endotoxin removal in the critically ill septic patient.