• Pietro Caironi, Roberto Latini, Joachim Struck, Oliver Hartmann, Andreas Bergmann, Giuseppe Maggio, Marco Cavana, Gianni Tognoni, Antonio Pesenti, Luciano Gattinoni, Serge Masson, and ALBIOS Study Investigators.
• 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.
• Chest. 2017 Aug 1; 152 (2): 312-320.

BackgroundThe 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.MethodsPlasma 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.ResultsPlasma 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.ConclusionsIn 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 RegistryClinicalTrials.gov; No.: NCT00707122.Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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