Endotoxin removal in cardiac bypass surgery in 2026: where do we stand, and where are we going?

The significance of endotoxemia during cardiopulmonary bypass remains incompletely understood. This review summarizes decades of research and highlights that clinically relevant endotoxemia affects only a subset of patients, making indiscriminate endotoxin-targeted therapies unlikely to provide meaningful benefit. Future research should therefore focus on identifying high-risk phenotypes, refining endotoxin assessment, and developing personalized therapeutics. Key priorities include standardization of endotoxin measurement, source tracking, gut barrier dysfunction, bypass-related factors, immunological profiling, EndoCAb-guided risk stratification, novel pharmacological approaches, and extracorporeal endotoxin removal. Regarding patient selection for therapeutic intervention, two high-risk subgroups warrant consideration. First, patients with EAA values >0.40 may be considered biologically exposed, while those with EAA values >0.60 represent a subgroup with endotoxin activity approaching levels seen in severe systemic inflammation or sepsis. Importantly, endotoxin activity must always be interpreted in relation to the host's neutralizing capacity. Second, reduced EndoCAb levels independently predict adverse outcomes after cardiac surgery, including prolonged mechanical ventilation, postoperative complications, and extended hospitalization. These patients may be particularly vulnerable to even moderate endotoxin exposure due to impaired endogenous neutralization. Precision medicine strategies targeting these identifiable subgroups represent the most promising path forward.