title: Copeptin levels are associated with organ dysfunction and death in the intensive care unit after out-of-hospital cardiac arrest.
abstract: BACKGROUND
  We studied associations of the stress hormones copeptin and cortisol with outcome and organ dysfunction after out-of-hospital cardiac arrest (OHCA).
  
  
  METHODS
  Plasma was obtained after consent from next of kin in the FINNRESUSCI study conducted in 21 Finnish intensive care units (ICUs) between 2010 and 2011. We measured plasma copeptin (pmol/L) and free cortisol (nmol/L) on ICU admission (245 patients) and at 48 hours (additional 33 patients). Organ dysfunction was categorised with 24-hour Sequential Organ Failure Assessment (SOFA) scores. Twelve-month neurological outcome (available in 276 patients) was classified with cerebral performance categories (CPC) and dichotomised into good (CPC 1 or 2) or poor (CPC 3 to 5). Data are presented as medians and interquartile ranges (IQRs). A Mann-Whitney U test, multiple linear and logistic regression tests with odds ratios (ORs) 95% confidence intervals (CIs) and beta (B) values, repeated measure analysis of variance, and receiver operating characteristic curves with area under the curve (AUC) were performed.
  
  
  RESULTS
  Patients with a poor 12-month outcome had higher levels of admission copeptin (89, IQR 41 to 193 versus 51, IQR 29 to 111 pmol/L, P = 0.0014) and cortisol (728, IQR 522 to 1,017 versus 576, IQR 355 to 850 nmol/L, P = 0.0013). Copeptin levels fell between admission and 48 hours (P <0.001), independently of outcome (P = 0.847). Cortisol levels did not change between admission and 48 hours (P = 0.313), independently of outcome (P = 0.221). The AUC for predicting long-term outcome was weak for copeptin (0.62, 95% CI 0.55 to 0.69) and cortisol (0.62, 95% CI 0.54 to 0.69). With logistic regression, admission copeptin (standard deviation (SD) increase OR 1.4, 95% CI 1.03 to 1.98) and cortisol (SD increase OR 1.5, 95% CI 1.1 to 2.0) predicted ICU mortality but not 12-month outcome. Admission factors correlating with SOFA were shockable rhythm (B -1.3, 95% CI -2.2 to -0.5), adrenaline use (B 1.1, 95% CI 0.2 to 2.0), therapeutic hypothermia (B 1.3 95% CI 0.4-2.2), and copeptin (B 0.04, 95% CI 0.02 to 0.07).
  
  
  CONCLUSIONS
  Admission copeptin and free cortisol were not of prognostic value regarding 12-month neurological outcome after OHCA. Higher admission copeptin and cortisol were associated with ICU death, and copeptin predicted subsequent organ dysfunction.
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milano, Milan, Italy. gristag@gmail.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ristagno
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milano, Milan, Italy. roberto.latini@marionegri.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.affiliation: Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, 35128, Padova, Italy. mario.plebani@unipd.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Department of Laboratory Medicine, University-Hospital of Padova, Via Giustiniani 2, 35128, Padova, Italy. martina.zaninotto@sanita.padova.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Zaninotto
authors.affiliation: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. jukka.vaahersalo@hus.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Vaahersalo
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milano, Milan, Italy. serge.masson@marionegri.it.
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.affiliation: Department of Neurology, Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. marjaana.tiainen@hus.fi.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Tiainen
authors.affiliation: Centre for Prehospital Emergency Care, Kuopio University Hospital, P.O. Box 100, FI 70029, Kuopio, Finland. jouni.kurola@kuh.fi.
authors.forename: Jouni
authors.initials: J
authors.lastname: Kurola
authors.affiliation: Laboratory of Pharmacokinetics and Clinical Chemistry, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Villa Camozzi, 24020, Ranica, Italy. flavio.gaspari@marionegri.it.
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 - 20156 Milano, Milan, Italy. valentina.milani@marionegri.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Milani
authors.affiliation: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. ville.pettila@hus.fi.
authors.forename: Ville
authors.initials: V
authors.lastname: Pettilä
authors.affiliation: Division of Intensive Care Medicine, Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland. markus.skrifvars@hus.fi.
authors.forename: Markus Benedikt
authors.initials: MB
authors.lastname: Skrifvars
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D017052:Hospital Mortality; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007036:Hypothermia, Induced / Q000379:methods / Q000401:mortality; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D058687:Out-of-Hospital Cardiac Arrest / Q000097:blood / Q000150:complications / Q000401:mortality*; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; C048197:copeptins; D006854:Hydrocortisone