Pietro Caironi1, Roberto Latini2, Joachim Struck3, Oliver Hartmann3, Andreas Bergmann3, Giuseppe Maggio4, Marco Cavana5, Gianni Tognoni2, Antonio Pesenti1, Luciano Gattinoni6, Serge Masson7. 1. Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; Dipartimento di Anestesia, Rianimazione, ed Emergenza Urgenza, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy. 2. Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy. 3. Sphingotec GmbH, Hennigsdorf, Germany. 4. IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. 5. Azienda USL U. Parini Valle d'Aosta, Aosta, Italy. 6. Department of Anesthesiology and Intensive Care Medicine, Georg-August-University Göttingen, Göttingen, Germany. 7. Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy. Electronic address: serge.masson@marionegri.it.
Abstract
BACKGROUND: The biological role of adrenomedullin (ADM), a hormone involved in hemodynamic homeostasis, is controversial in sepsis because administration of either the peptide or an antibody against it may be beneficial. METHODS: Plasma biologically active ADM (bio-ADM) was assessed on days 1, 2, and 7 after randomization of 956 patients with sepsis or septic shock to albumin or crystalloids for fluid resuscitation in the multicenter Albumin Italian Outcome Sepsis trial. We tested the association of bio-ADM and its time-dependent variation with fluid therapy, vasopressor administration, organ failures, and mortality. RESULTS: Plasma bio-ADM on day 1 (median [Q1-Q3], 110 [59-198] pg/mL) was higher in patients with septic shock, associated with 90-day mortality, multiple organ failures and the average extent of hemodynamic support therapy (fluids and vasopressors), and serum lactate time course over the first week. Moreover, it predicted incident cardiovascular dysfunction in patients without shock at enrollment (OR [95% CI], 1.9 [1.4-2.5]; P < .0001, for an increase of 1 interquartile range of bio-ADM concentration). bio-ADM trajectory during the first week of treatment clearly predicted 90-day mortality after adjustment for clinically relevant covariates (hazard ratio [95% CI], 1.3 [1.2-1.4]; P < .0001), and its reduction below 110 pg/mL at day 7 was associated with a marked reduction in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were not dependent on albumin treatment. CONCLUSIONS: In patients with sepsis, the circulating, biologically active form of ADM may help individualizing hemodynamic support therapy, while avoiding harmful effects. Its possible pathophysiologic role makes bio-ADM a potential candidate for future targeted therapies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00707122.
BACKGROUND: The biological role of adrenomedullin (ADM), a hormone involved in hemodynamic homeostasis, is controversial in sepsis because administration of either the peptide or an antibody against it may be beneficial. METHODS: Plasma biologically active ADM (bio-ADM) was assessed on days 1, 2, and 7 after randomization of 956 patients with sepsis or septic shock to albumin or crystalloids for fluid resuscitation in the multicenter Albumin Italian Outcome Sepsis trial. We tested the association of bio-ADM and its time-dependent variation with fluid therapy, vasopressor administration, organ failures, and mortality. RESULTS: Plasma bio-ADM on day 1 (median [Q1-Q3], 110 [59-198] pg/mL) was higher in patients with septic shock, associated with 90-day mortality, multiple organ failures and the average extent of hemodynamic support therapy (fluids and vasopressors), and serum lactate time course over the first week. Moreover, it predicted incident cardiovascular dysfunction in patients without shock at enrollment (OR [95% CI], 1.9 [1.4-2.5]; P < .0001, for an increase of 1 interquartile range of bio-ADM concentration). bio-ADM trajectory during the first week of treatment clearly predicted 90-day mortality after adjustment for clinically relevant covariates (hazard ratio [95% CI], 1.3 [1.2-1.4]; P < .0001), and its reduction below 110 pg/mL at day 7 was associated with a marked reduction in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were not dependent on albumin treatment. CONCLUSIONS: In patients with sepsis, the circulating, biologically active form of ADM may help individualizing hemodynamic support therapy, while avoiding harmful effects. Its possible pathophysiologic role makes bio-ADM a potential candidate for future targeted therapies. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00707122.
Authors: Christopher Geven; Dirk van Lier; Alice Blet; Roel Peelen; Bas Ten Elzen; Alexandre Mebazaa; Matthijs Kox; Peter Pickkers Journal: Br J Clin Pharmacol Date: 2018-07-03 Impact factor: 4.335
Authors: Eva M Boorsma; Jozine M Ter Maaten; Kevin Damman; Wilfried Dinh; Finn Gustafsson; Steven Goldsmith; Daniel Burkhoff; Faiez Zannad; James E Udelson; Adriaan A Voors Journal: Nat Rev Cardiol Date: 2020-05-15 Impact factor: 32.419
Authors: Alexandre Mebazaa; Christopher Geven; Alexa Hollinger; Xavier Wittebole; Benjamin Glen Chousterman; Alice Blet; Etienne Gayat; Oliver Hartmann; Paul Scigalla; Joachim Struck; Andreas Bergmann; Massimo Antonelli; Albertus Beishuizen; Jean-Michel Constantin; Charles Damoisel; Nicolas Deye; Salvatore Di Somma; Thierry Dugernier; Bruno François; Stephane Gaudry; Vincent Huberlant; Jean-Baptiste Lascarrou; Gernot Marx; Emmanuelle Mercier; Haikel Oueslati; Peter Pickkers; Romain Sonneville; Matthieu Legrand; Pierre-François Laterre Journal: Crit Care Date: 2018-12-21 Impact factor: 9.097
Authors: Oscar H M Lundberg; Maria Lengquist; Martin Spångfors; Martin Annborn; Deborah Bergmann; Janin Schulte; Helena Levin; Olle Melander; Attila Frigyesi; Hans Friberg Journal: Crit Care Date: 2020-11-04 Impact factor: 9.097