Arianna Piotti1, Deborah Novelli2, Jennifer Marie Theresia Anna Meessen2, Daniela Ferlicca3, Sara Coppolecchia4, Antonella Marino5, Giovanni Salati6, Monica Savioli7, Giacomo Grasselli7, Giacomo Bellani3,8, Antonio Pesenti7, Serge Masson2, Pietro Caironi9,10, Luciano Gattinoni11, Marco Gobbi1, Claudia Fracasso1, Roberto Latini12. 1. Department of Biochemistry and Molecular Pharmacology, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy. 2. Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS, Via Mario Negri 2, 20156, Milan, Italy. 3. Emergency Department, Ospedale San Gerardo, Monza, Italy. 4. Anestesia E Rianimazione, ISMETT IRCCS, Palermo, Italy. 5. Anestesia III Terapia Intensiva Adulti, ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy. 6. UOC Anestesia E Rianimazione, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. 7. Dipartimento Di Anestesia, Rianimazione Ed Emergenza Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy. 9. Department of Anesthesiology and Critical Care, AOU S. Luigi Gonzaga, Orbassano, Italy. 10. Department of Oncology, Università Degli Studi Di Torino, Turin, Italy. 11. Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Gӧttingen, Gӧttingen, Germany. 12. Department of Cardiovascular Medicine, Mario Negri Institute for Pharmacological Research IRCCS, Via Mario Negri 2, 20156, Milan, Italy. roberto.latini@marionegri.it.
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.
RCT Entities:
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 shockpatients. 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.
Authors: H Ait-Oufella; N Bige; P Y Boelle; C Pichereau; M Alves; R Bertinchamp; J L Baudel; A Galbois; E Maury; B Guidet Journal: Intensive Care Med Date: 2014-05-09 Impact factor: 17.440