Endotoxemic Shock: A Molecular Phenotype in Sepsis

BACKGROUND: Marked heterogeneity exists among patients with sepsis, both in terms of distribution of organ dysfunction and its severity. Such heterogeneity could be explained by the presence of multiple subtypes of sepsis that may have important implications for treatment. METHODS: Narrative review of published literature involving endotoxin from 1970 to 2022. RESULTS: In humans, endotoxemia is most consistently associated with a specific pattern of organ failure including shock, endothelial dysfunction, acute kidney injury, and hepatic dysfunction. This pattern is consistent with complement activation and uncontrolled inflammation, two features of endotoxemia. Unbiased discovery using artificial intelligence also identifies a subtype of sepsis which features these same organ failures. CONCLUSION: Endotoxin appears to represent an important molecular phenotype of sepsis with unique clinical features and high mortality.