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Crit Care. 2018 Dec 21;22(1):354. doi: 10.1186/s13054-018-2243-2.

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study.

Collaborators (272)

Laterre PF, Berghe C, Dujardin MF, Renard S, Wittebole X, Collienne C, Zapatero DC, Dugernier T, Vinetti M, De Schryver N, Thirifays A, Mairesse J, Huberlant V, Petre H, Buelens I, Henin P, Trine H, Laurent Y, Sébastien L, Geukens P, Kehl L, François B, Vignon P, Pichon N, Begot E, Fedou AL, Chapellas C, Galy A, Rodier N, Baudrillart L, Nouaille M, Laleu S, Mancia C, Daix T, Bourzeix P, Herafa I, Duchambon AA, Lascarrou JB, Fiancette M, Colin G, Henry-Lagarrigue M, Lacherade JC, Lebert C, Martin-Levèvre L, Vinatier I, Yehia A, Bachoumas K, Joret A, Reignier J, Rousseau C, Maquigneau N, Alcourt Y, Zinzonni VE, Deschamps A, Robert A, Mercier E, Simeon-Vieules V, Aubrey A, Mabilat C, Garot D, Ehrmann S, Legras A, Manikikian, Jouan Y, Dequin PF, Guillon A, Bodet-Contentin L, Rouve E, Salmon C, Brick L, Massat S, Desachy A, Fally MA, Robin L, Cracco C, Lafon C, Calvat S, Rouleau S, Schnell D, Lasocki S, Fesard P, Leblanc D, Bouhours G, Chassier C, Conte M, Gaillard T, Denou F, Kerymel M, Guyon M, Loiez A, Lebreton S, Meziani F, Allam H, Chenaf S, Rahmani H, Heenen S, Kummerlen C, Delabranche X, Boivin A, Clere-Jehl R, Rabouël Y, Pottecher J, Bayer S, Metzger C, Hecketsweiler S, Ludes PO, Besancenot H, Dhif N, Freys G, Lessinger JM, Launoy A, Ruimy A, Meyer A, Szozot M, Mebazaa A, Deye N, Gayat E, Fournier MC, Abroug S, Louadah B, Feliot E, Voicu S, Malissin I, Megarbane B, Manivet P, Victori G, Kelly DS, La Foucher B, Pierre V, Kerdjana L, Beeken T, Goury A, Garcon P, Gaugain S, Chousterman BG, Huot B, Barthelemy R, Soyer B, Jacob L, Legrand M, Fournier MC, Bonnet F, Legall C, Oueslati H, Cupaciu A, Manivet P, Louadah B, Sonneville R, Letrou S, Bouadma L, Mourvillier B, Deiler V, Magalhaes E, Neuville M, Timsit JF, Radjou A, Gaudry S, Dubief E, Messika J, La Combe B, Roux D, Berquier G, Laissi M, Ricard JD, Constantin JM, Perbet S, Delmas J, Pascal J, Cayot S, Guerin R, Jabaudon M, Roszyk L, Rolhion C, Bourdier J, Lematte M, Gouhier C, Verlhac C, Godet T, Radji S, Caumon E, Thibault S, Marx N, Schuerholz T, Pezechk J, Feld F, Brülls C, Beeker T, Simon TP, Deisz R, Schindler A, Meier B, Janisch T, Hohn A, Schedler D, Wetsch W, Schröder D, Meier-Hellmann A, Lucht A, Henker R, Römmer M, Meinig T, Zacharowski KD, Meybohm P, Lindau S, Mutlak H, Kluge S, Ringeis G, Füllekrug B, Singer B, Nierhaus A, Bangert K, de Heer G, Frings D, Fuhrmann V, Müller J, Schreiber J, Sensen B, Siedler S, Siewecke A, Söffker G, Wichmann D, Kerinn M, Jaschinski U, Kreuser I, Zanquila M, Kortgen A, Bloos F, Gonnert F, Thomas-Rüddel D, Haucke A, Kolanos S, Kohlberg KK, Bloos P, Schwope K, Di Somma S, Rossella M, Russo V, Simona S, Bartoli C, Navarin S, Bongiovanni C, Orru M, Quatrocchi D, Zoccoli G, Varchetta A, Antonelli M, de Pascale G, Vallecoccia MS, Cutuli SL, Digravio V, Quattrochi D, D'Arrigo S, Leone FE, Beishuizen B, Rinket M, Border N, Bos-Burgmeijer M, Braad A, Papendorp S, Cornet A, Vermeijden J, Trof RJ, Pickkers P, van de A M, Van Wezel H, Heunks L, Border N, Luijten-Arts C, Hoedemaekers A, van der Hoeven H, Roovers N, Hemelaar P.

Author information

1
Department of Anesthesiology, Burn and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, 2 rue A. Paré, 75010, Paris, France.
2
Inserm 942, Paris, France.
3
University Paris Diderot, Paris, France.
4
Department of Intensive Care Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6500, HB, Nijmegen, The Netherlands.
5
Department of Anesthesiology, Burn and Critical Care Medicine, AP-HP, Saint Louis and Lariboisière University Hospitals, 2 rue A. Paré, 75010, Paris, France. alexa.hollinger@usb.ch.
6
Inserm 942, Paris, France. alexa.hollinger@usb.ch.
7
Department of Anesthesia, Surgical Intensive Care, Prehospital Emergency Medicine and Pain Therapy, University Hospital Basel, Basel, Switzerland. alexa.hollinger@usb.ch.
8
Department of Critical Care Medicine, St Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium.
9
sphingotec GmbH, Hennigsdorf, Germany.
10
Adrenomed AG, Hennigsdorf, Germany.
11
Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
12
Department of Intensive Care, Medische Spectrum Twente, Enschede, The Netherlands.
13
Department of Perioperative Medicine, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
14
CHU de Tours, Tours, France.
15
Sant' Andrea Hospital, Rome, Italy.
16
Clinique St Pierre, Ottignies, Belgium.
17
ICU Department, CHU Dupuytren, Limoges, France.
18
INSERM CIC 1435/UMR 1092, Limoges, France.
19
Hôpital Louis Mourier, Colombes, France.
20
Hôpital Jolimont, Haine-St-Paul, Belgium.
21
Centre Hospitalier Universitaire de Nantes, Nantes, France.
22
Klinik für Operative Intensivmedizin und Intermediate Care, Universitätsklinikum der RWTH, Aachen, Germany.
23
Hopital Bichat Claude-Bernard, Paris, France.
24
Department of Critical Care Medicine, Saint Luc University Hospital, Université Catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium.

Abstract

BACKGROUND:

Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial.

METHODS:

AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock.

RESULTS:

Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8).

CONCLUSIONS:

AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015.

KEYWORDS:

Biomarker; Outcome; Sepsis-2; Sepsis-3

PMID:
30583748
PMCID:
PMC6305573
DOI:
10.1186/s13054-018-2243-2
[Indexed for MEDLINE]
Free PMC Article

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