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Original Research |

Circulating biologically active adrenomedullin (bio-ADM) predicts hemodynamic support requirement and mortality during sepsis

Pietro Caironi, MD; Roberto Latini, MD; Joachim Struck, PhD; Oliver Hartmann, MS; Andreas Bergmann, PhD; Giuseppe Maggio, MD; Marco Cavana, MD; Gianni Tognoni, MD; Antonio Pesenti, MD; Luciano Gattinoni, MD; Serge Masson, PhD
Author and Funding Information

Conflicts of interest: AB is CEO of Sphingotec GmbH, and JS and OH are employees at Sphingotec GmbH, the manufacturer of bio-adrenomedullin reagents. The institutions of PC, RL, GT, AP and SM received a modest research grant from Sphingotec GmbH. The remaining authors declare no conflict of interest.

Clinical Trial Registration: ALBIOS trial ClinicalTrials.gov number, NCT00707122.

aDipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

bDipartimento di Anestesia, Rianimazione, ed Emergenza Urgenza, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, Milan, Italy

cDepartment of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy

dSphingotec GmbH, Hennigsdorf, Germany

eIRCCS Fondazione Policlinico San Matteo, Pavia, Italy

fAzienda USL U. Parini Valle d’Aosta, Aosta, Italy

gDepartment of Anesthesiology and Intensive Care Medicine, Georg-August-University Göttingen, Göttingen, Germany

Correspondence: Dr Serge Masson, Istituto “Mario Negri”, via Privata Giuseppe La Masa 19, 20156 Milan, Italy.


Copyright 2017, . All Rights Reserved.


Chest. 2017. doi:10.1016/j.chest.2017.03.035
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Abstract

Background  The biological role of adrenomedullin, a hormone involved in hemodynamic homeostasis, is controversial in sepsis, since administration of either the peptide or an antibody against it may be beneficial.

Methods  Plasma 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 (ALBIOS) 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<0.0001, 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 (HR [95% CI] 1.3 [1.2-1.4], p<0.0001), and its reduction below 110 pg/mL at day 7 was associated to 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 adrenomedullin may help individualizing hemodynamic support therapy, while avoiding harmful effects. Its possible pathophysiologic role makes bio-ADM a potential candidate for future targeted therapies.


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