Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS
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,
the ALBIOS Investigators
Affiliations
Arianna Piotti
Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS
Deborah Novelli
Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS
Jennifer Marie Theresia Anna Meessen
Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS
Daniela Ferlicca
Emergency Department, Ospedale San Gerardo
Sara Coppolecchia
Anestesia E Rianimazione, ISMETT IRCCS
Antonella Marino
Anestesia III Terapia Intensiva Adulti, ASST Ospedale Papa Giovanni XXIII
Giovanni Salati
UOC Anestesia E Rianimazione, IRCCS Arcispedale Santa Maria Nuova
Monica Savioli
Dipartimento Di Anestesia, Rianimazione Ed Emergenza Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Giacomo Grasselli
Dipartimento Di Anestesia, Rianimazione Ed Emergenza Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Giacomo Bellani
Emergency Department, Ospedale San Gerardo
Antonio Pesenti
Dipartimento Di Anestesia, Rianimazione Ed Emergenza Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico
Serge Masson
Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS
Pietro Caironi
Department of Anesthesiology and Critical Care, AOU S. Luigi Gonzaga
Luciano Gattinoni
Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Gӧttingen
Marco Gobbi
Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS
Claudia Fracasso
Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS
Roberto Latini
Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS
Abstract Background Septic 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. Methods This 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. Results Plasma 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. Conclusion Circulating 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 Registration: ALBIOS ClinicalTrials.gov number NCT00707122.