Mid-Regional Pro-Adrenomedullin as a Translational Biomarker of Microcirculatory Dysfunction in Sepsis: A Prospective Observational Study

<b>Background/Objectives</b>: Mid-regional pro-adrenomedullin (MR-proADM) is a biomarker of endothelial dysfunction in sepsis. Its relationship with real-time microcirculatory alterations in critically ill patients remains insufficiently characterised. <b>Methods</b>: In a prospective cohort of 59 ICU patients with sepsis, serial sublingual microcirculation assessments were performed using sidestream dark field (SDF) imaging. Serum MR-proADM concentrations were measured with BRAHMS Kryptor assays. Automated software quantified microvascular structure and flow. Associations with disease severity and outcomes were evaluated using correlation, regression, and receiver operating characteristic (ROC) analyses (ClinicalTrials.gov Identifier: NCT05357339). <b>Results</b>: Higher MR-proADM concentrations at ICU admission were modestly associated with impaired microvascular perfusion (perfused number of crossings [PNOC]: ρ = -0.32; perfused De Backer density [PDBD]: ρ = -0.32; consensus proportion of perfused vessels [CPPV]: ρ = -0.26; all <i>p</i> < 0.05). Rising MR-proADM levels over time were strongly associated with worsening perfusion (ΔPDBD: ρ = 0.52; ΔPNOC: ρ = 0.54). MR-proADM correlated with SOFA and APACHE II scores and predicted the need for renal replacement therapy (AUC = 0.799, <i>p</i> = 0.041), but not ICU length of stay or hospital mortality. <b>Conclusions</b>: MR-proADM correlates with in vivo microcirculatory dysfunction in sepsis. Its dynamic association with microvascular impairment supports its potential role as a translational biomarker for monitoring endothelial and microcirculatory failure in critically ill patients.