title: Current real-life use of vasopressors and inotropes in cardiogenic shock - adrenaline use is associated with excess organ injury and mortality.
abstract: BACKGROUND
  Vasopressors and inotropes remain a cornerstone in stabilization of the severely impaired hemodynamics and cardiac output in cardiogenic shock (CS). The aim of this study was to analyze current real-life use of these medications, and their impact on outcome and on changes in cardiac and renal biomarkers over time in CS.
  
  
  METHODS
  The multinational CardShock study prospectively enrolled 219 patients with CS. The use of vasopressors and inotropes was analyzed in relation to the primary outcome, i.e., 90-day mortality, with propensity score methods in 216 patients with follow-up data available. Changes in cardiac and renal biomarkers over time until 96 hours from baseline were analyzed with linear mixed modeling.
  
  
  RESULTS
  Patients were 67 (SD 12) years old, 26 % were women, and 28 % had been resuscitated from cardiac arrest prior to inclusion. On average, systolic blood pressure was 78 (14) and mean arterial pressure 57 (11) mmHg at detection of shock. 90-day mortality was 41 %. Vasopressors and/or inotropes were administered to 94 % of patients and initiated principally within the first 24 hours. Noradrenaline and adrenaline were given to 75 % and 21 % of patients, and 30 % received several vasopressors. In multivariable logistic regression, only adrenaline (21 %) was independently associated with increased 90-day mortality (OR 5.2, 95 % CI 1.88, 14.7, p = 0.002). The result was independent of prior cardiac arrest (39 % of patients treated with adrenaline), and the association remained in propensity-score-adjusted analysis among vasopressor-treated patients (OR 3.0, 95 % CI 1.3, 7.2, p = 0.013); this was further confirmed by propensity-score-matched analysis. Adrenaline was also associated, independent of prior cardiac arrest, with marked worsening of cardiac and renal biomarkers during the first days. Dobutamine and levosimendan were the most commonly used inotropes (49 % and 24 %). There were no differences in mortality, whether noradrenaline was combined with dobutamine or levosimendan.
  
  
  CONCLUSIONS
  Among vasopressors and inotropes, adrenaline was independently associated with 90-day mortality in CS. Moreover, adrenaline use was associated with marked worsening in cardiac and renal biomarkers. The combined use of noradrenaline with either dobutamine or levosimendan appeared prognostically similar.
authors.affiliation: Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, PO Box 340, 00029 HUS, Helsinki, Finland. tuukka.tarvasmaki@fimnet.fi.
authors.forename: Tuukka
authors.identifier: http://orcid.org/0000-0003-3406-243X
authors.initials: T
authors.lastname: Tarvasmäki
authors.affiliation: Division of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Johan
authors.initials: J
authors.lastname: Lassus
authors.affiliation: Division of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Marjut
authors.initials: M
authors.lastname: Varpula
authors.affiliation: Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sionis
authors.affiliation: Department of Social Research, Faculty of Social Sciences, Centre for Research Methods, University of Helsinki, Helsinki, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Sund
authors.affiliation: Rigshospitalet, Copenhagen University Hospital, Division of Heart Failure, Pulmonary Hypertension and Heart Transplantation, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Department of Internal Medicine and Cardiology, University Hospital Brno, Brno, Czech Republic.
authors.forename: Jindrich
authors.initials: J
authors.lastname: Spinar
authors.affiliation: Heart Failure Clinic and Secondary Cardiology Department, Attikon University Hospital, Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.affiliation: Institute of Cardiology, Intensive Cardiac Therapy Clinic, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Banaszewski
authors.affiliation: Department of Cardiology, University of Porto, CINTESIS, Porto Medical School, São João Hospital Center, Porto, Portugal.
authors.forename: Jose
authors.initials: J
authors.lastname: Silva Cardoso
authors.affiliation: Division of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Brescia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carubelli
authors.affiliation: Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Medicine Sant'Andrea Hospital, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Di Somma
authors.affiliation: INSERM U942, Hopital Lariboisiere, APHP and University Paris Diderot, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.affiliation: Emergency Medicine, University of Helsinki and Department of Emergency Medicine and Services, Helsinki University Hospital, PO Box 340, 00029 HUS, Helsinki, Finland.
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Harjola
mesh_terms: D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D004837:Epinephrine / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D012770:Shock, Cardiogenic / Q000150:complications / Q000188:drug therapy*; D014022:Tissue Survival / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D004837:Epinephrine
keywords: Adrenaline; Cardiogenic shock; Inotropes; Mortality; Propensity score; Survival; Vasoactive medication; Vasopressors