ENDOTHELIAL INJURY MARKERS AS PROGNOSTIC PREDICTORS IN CRITICALLY ILL PATIENTS: A REVIEW OF RECENT CLINICAL EVIDENCE
DOI:
https://doi.org/10.56238/levv17n58-042Keywords:
Sepsis, Septic Shock, Endothelium, BiomarkersAbstract
Introduction: Sepsis and septic shock remain associated with high mortality in intensive care, and endothelial dysfunction plays a central role in the pathophysiology of organ failure. Biomarkers of endothelial injury have been investigated as tools for prognostic stratification and early identification of high-risk patients. However, methodological heterogeneity and the lack of standardized cutoff values hinder their routine clinical application.
Objective: To systematically and critically evaluate the association between biomarkers of endothelial dysfunction and mortality in adult patients with sepsis or septic shock, based on recent clinical evidence published over the last five years. Secondary objectives were to identify the biomarkers most consistently associated with mortality, compare their prognostic performance with the Sequential Organ Failure Assessment and lactate, analyze the impact of single versus serial measurement, explore sources of methodological heterogeneity, and estimate certainty of evidence using standardized instruments.
Methods: A search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP, without language restriction, prioritizing human studies published within the last five years. Clinical studies in adults with sepsis or septic shock that measured at least one endothelial biomarker and reported its association with mortality were included. Risk of bias was assessed using RoB 2, ROBINS-I, and QUADAS-2 according to study design, and certainty of evidence was estimated using GRADE, with predominantly qualitative synthesis and meta-analysis only when sufficient homogeneity was present.
Results and Discussion: Twenty studies were included in the qualitative synthesis. Syndecan-1 and angiopoietin-2 were the biomarkers most frequently associated with higher mortality and greater severity, whereas endocan and soluble thrombomodulin showed variable performance, influenced by timing of collection and clinical context. Studies using serial measurements suggested a potential advantage of temporal trajectories for risk discrimination, but comparability was limited by heterogeneity in clinical definitions, analytical platforms, and outcomes. Certainty of evidence ranged from low to moderate, mainly because of the predominance of observational studies, risk of confounding, and inconsistency across studies.
Conclusion: Biomarkers of endothelial injury, especially syndecan-1 and angiopoietin-2, are consistently associated with worse prognosis in sepsis and septic shock and may complement clinical scores and lactate in risk stratification. Broad clinical implementation still depends on analytical standardization, definition of cutoff values, and external validation, in addition to pragmatic studies demonstrating incremental clinical benefit in biomarker-guided algorithms.
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