Plasma Endocan Levels Are Associated With Organ Dysfunction, Fluid Accumulation and Poor Outcome in Sepsis Patients With Acute Respiratory Failure

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Abstract BATIONALE: Widespread endothelial dysfunction and injury are pivotal in the pathogenesis of sepsis, resulting in vascular hyperpermeability, hypotension, and organ dysfunction. Endocan, also known as endothelial-specific molecule-1, is a soluble dermatan sulfate proteoglycan secreted predominantly by activated endothelial cells. Endocan expression is upregulated by pro-inflammatory cytokines such as TNF-alpha and IL-1beta that have also been implicated in the pathogenesis of sepsis. Although endocan has been studied as a biomarker in various diseases including malignancy and atherosclerosis, it is unknown whether plasma endocan is as a marker for endothelial hyperpermeability, organ dysfunction, or clinical outcomes in sepsis. METHODS: This prospective observational study involved 243 ICU patients with sepsis, acute respiratory failure, and an APACHE-II score of 25 or higher. Plasma endocan levels were measured on day 1 after enrollment by ELISA. The primary objective of the study was to test the association between plasma endocan levels and the development of organ dysfunction (as defined by the Brussels organ failure criteria), fluid accumulation, and in-hospital mortality. The secondary objective was to determine whether plasma endocan levels could independently predict clinical outcomes in patients with septic shock. RESULTS: Patients with sepsis and acute respiratory failure who died during hospitalization had notably higher plasma endocan levels compared to survivors (3.11 ng/ml, IQR 2.00 – 5.40 ng/ml vs. 2.25 ng/ml, IQR 1.18 – 4.32 ng/ml, p = 0.002). Multivariable logistic regression analysis indicated that plasma endocan levels are an independent predictor of hospital mortality. Furthermore, higher plasma endocan levels by quartile were strongly linked with APACHE scores (p = 0.026), circulatory failure (p = 0.006), and renal failure at enrollment (p = 0.008) (Figure A-C). Elevated plasma endocan levels were also significantly associated with a positive net fluid balance on ICU admission day (p = 0.002) and in the subsequent 24 (p < 0.001), 48 (p < 0.001), and 72 (p < 0.001) hours after enrollment (Figure D-F). Additionally, plasma endocan levels were an independent predictor of mortality in the subset of patients with septic shock. CONCLUSIONS: Endocan is a robust predictor of clinical outcomes and organ dysfunction in sepsis and septic shock patients with acute respiratory failure. Whether endocan is simply a marker of endothelial activation and injury or contributes to the pathophysiology of organ dysfunction in sepsis is an important topic for future research.

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