Assessing vascular barrier permeability in critically ill patients: what are we really measuring?

Perturbation of vascular barrier permeability is a central mechanism in the pathophysiology of critical illness, contributing to tissue edema, impaired oxygen diffusion, and organ dysfunction. Despite advances in the field, direct bedside assessment of vascular permeability remains unavailable. Current approaches rely on indirect and compartment-specific surrogates, raising important questions about what is actually being measured. This narrative review summarizes the physiological principles underlying vascular barrier function and its disruption in conditions such as sepsis, acute respiratory distress syndrome, and major surgery. Currently available bedside tools used to assess vascular permeability or its consequences are critically appraised, including clinical examination, ultrasonography, transpulmonary thermodilution, bioelectrical impedance analysis, circulating biomarkers of endothelial injury (e.g., glycocalyx degradation products, angiopoietin-2), and albumin kinetics–based methods. While these techniques provide valuable insights, they predominantly reflect downstream consequences such as tissue edema, intravascular volume shifts, or endothelial activation rather than permeability itself. In addition, vascular permeability is a dynamic, context-dependent, and organ-specific process influenced by inflammatory, hemodynamic, and therapeutic factors, further complicating its interpretation. Each method therefore captures only a partial dimension of vascular barrier dysfunction, with important limitations related to specificity, feasibility, validation and standardization. No single bedside tool currently provides a comprehensive assessment of vascular permeability in critically ill patients. A multimodal approach integrating clinical evaluation, imaging, hemodynamic monitoring, and biomarkers is required to better characterize vascular barrier dysfunction. Future research should focus on validating composite indices and developing reliable, real-time bedside tools capable of directly assessing vascular permeability, with the ultimate goal of improving risk stratification and guiding personalized therapeutic strategies.