• Arianna Piotti, Deborah Novelli, Jennifer Marie Theresia Anna Meessen, Daniela Ferlicca, Sara Coppolecchia, Antonella Marino, Giovanni Salati, Monica Savioli, Giacomo Grasselli, Giacomo Bellani, Antonio Pesenti, Serge Masson, Pietro Caironi, Luciano Gattinoni, Marco Gobbi, Claudia Fracasso, Roberto Latini, and ALBIOS Investigators.
• Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy.
• Crit Care. 2021 Mar 19; 25 (1): 113.

BackgroundSeptic shock is characterized by breakdown of the endothelial glycocalyx and endothelial damage, contributing to fluid extravasation, organ failure and death. Albumin has shown benefit in septic shock patients. Our aims were: (1) to identify the relations between circulating levels of syndecan-1 (SYN-1), sphingosine-1-phosphate (S1P) (endothelial glycocalyx), and VE-cadherin (endothelial cell junctions), severity of the disease, and survival; (2) to evaluate the effects of albumin supplementation on endothelial dysfunction in patients with septic shock.MethodsThis was a retrospective analysis of a multicenter randomized clinical trial on albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis Trial, ALBIOS). Concentrations of SYN-1, S1P, soluble VE-cadherin and other biomarkers were measured on days 1, 2 and 7 in 375 patients with septic shock surviving up to 7 days after randomization.ResultsPlasma concentrations of SYN-1 and VE-cadherin rose significantly over 7 days. SYN-1 and VE-cadherin were elevated in patients with organ failure, and S1P levels were lower. SYN-1 and VE-cadherin were independently associated with renal replacement therapy requirement during ICU stay, but only SYN-1 predicted its new occurrence. Both SYN-1 and S1P, but not VE-cadherin, predicted incident coagulation failure. Only SYN-1 independently predicted 90-day mortality. Albumin significantly reduced VE-cadherin, by 9.5% (p = 0.003) at all three time points.ConclusionCirculating components of the endothelial glycocalyx and of the endothelial cell junctions provide insights into severity and progression of septic shock, with special focus on incident coagulation and renal failure. Albumin supplementation lowered circulating VE-cadherin consistently over time.Clinical Trial RegistrationALBIOS ClinicalTrials.gov number NCT00707122.

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