Pär I Johansson1, Nicolai Haase2, Anders Perner2, Sisse R Ostrowski3. 1. Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Surgery, Division of Acute Care Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School at Houston, TX, USA. Electronic address: per.johansson@regionh.dk. 2. Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 3. Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract
PURPOSE: The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septic patients. MATERIALS AND METHODS:Septic patients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation. RESULTS:Sixty-seven patients were included, of whom 14 turned out to receivenoradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n=53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P<.05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P<.05), and 28- and 90-day mortality (P<.05). CONCLUSIONS: In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood.
RCT Entities:
PURPOSE: The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septicpatients. MATERIALS AND METHODS:Septicpatients included in the Scandinavian Starch for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation and damage, natural anticoagulation, fibrinolysis, cell damage, and platelet activation. RESULTS: Sixty-seven patients were included, of whom 14 turned out to receive noradrenaline infusion at blood sampling. These 14 patients had p-noradrenaline 5-fold higher than patients not receiving catecholamines (n=53), whereas no other baseline preintervention biomarkers differed. In the 53 patients not receiving catecholamines at blood sampling, endogenous p-noradrenaline correlated positively with adrenaline, syndecan 1, soluble vascular endothelial growth factor receptor 1, soluble CD40 ligand, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all P<.05) and was independently associated with syndecan 1, soluble vascular endothelial growth factor receptor 1, and PAI-1 (all P<.05), and 28- and 90-day mortality (P<.05). CONCLUSIONS: In septicpatients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarctionpatients. The catecholamine surge in critical illness may contribute to balance endothelial damage and procoagulation with hypocoagulability and hyperfibrinolysis in the circulating blood.
Authors: Danielle S Gruen; Joshua B Brown; Francis X Guyette; Yoram Vodovotz; Pär I Johansson; Jakob Stensballe; Derek A Barclay; Jinling Yin; Brian J Daley; Richard S Miller; Brian G Harbrecht; Jeffrey A Claridge; Herb A Phelan; Matthew D Neal; Brian S Zuckerbraun; Timothy R Billiar; Jason L Sperry Journal: JCI Insight Date: 2020-04-23
Authors: Sisse Rye Ostrowski; Nicolai Haase; Rasmus Beier Müller; Morten Hylander Møller; Frank Christian Pott; Anders Perner; Pär Ingemar Johansson Journal: Crit Care Date: 2015-04-24 Impact factor: 9.097
Authors: Anna Sina P Meyer; Sisse R Ostrowski; Jesper Kjaergaard; Pär I Johansson; Christian Hassager Journal: Trials Date: 2016-08-02 Impact factor: 2.279
Authors: Jungsil Lee; Young Jae Cho; Se Joong Kim; Ho Il Yoon; Jong Sun Park; Choon Taek Lee; Jae Ho Lee; Yeon Joo Lee Journal: J Korean Med Sci Date: 2017-03 Impact factor: 2.153
Authors: Alex P Di Battista; Sandro B Rizoli; Brandon Lejnieks; Arimie Min; Maria Y Shiu; Henry T Peng; Andrew J Baker; Michael G Hutchison; Nathan Churchill; Kenji Inaba; Bartolomeu B Nascimento; Airton Leonardo de Oliveira Manoel; Andrew Beckett; Shawn G Rhind Journal: Shock Date: 2016-09 Impact factor: 3.454