title: Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C.
abstract: OBJECTIVE
  Post-cardiac arrest syndrome (PCAS) is characterized by systemic inflammation, however data on the prognostic value of inflammatory markers is sparse. We sought to investigate the importance of systemic inflammation, assessed by interleukin-6 (IL-6) in comatose survivors of out-of-hospital cardiac arrest.
  
  
  METHODS
  A total of 682 patients enrolled in the Target Temperature Management (TTM) trial, surviving >24h with available IL-6 data were included. IL-6 was measured on days 1, 2 and 3 after return of spontaneous circulation. Severity of PCAS was assessed daily by the Sequential Organ Failure Assessment score. Survival status was recorded at 30 days.
  
  
  RESULTS
  High levels of IL-6 at day 1-3 (all p<0.0001) were independently associated with severity of PCAS with no interaction of target temperature (all p=NS). IL-6 levels did not differ between temperature groups (p(interaction)=0.99). IL-6 levels at day 2 (p<0.0001) and day 3 (p<0.0001) were associated with crude mortality. Adjusted Cox proportional-hazards analysis showed that a two-fold increase of IL-6 levels at day 2 (HR=1.15 (95% CI: 1.07-1.23), p=0.0002) and day 3 (HR=1.18 (95% CI: 1.09-1.27), p<0.0001) were associated with mortality. IL-6 levels at day 3 had the highest discriminative value in predicting mortality (AUC=0.66). IL-6 did not significantly improve 30-day mortality prediction compared to traditional prognostic factors (p=0.08).
  
  
  CONCLUSIONS
  In patients surviving >24h following cardiac arrest, IL-6 levels were significantly elevated and associated with severity of PCAS with no significant influence of target temperature. High IL-6 levels were associated with increased mortality. Measuring levels of IL-6 did not provide incremental prognostic value.
authors.affiliation: Department of Cardiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark. Electronic address: jbj@dadlnet.dk.
authors.forename: John
authors.initials: J
authors.lastname: Bro-Jeppesen
authors.affiliation: Department of Cardiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
authors.affiliation: Department of Anesthesia and Intensive Care, Centre Hospitalier de Luxembourg, Luxembourg.
authors.forename: Pascal
authors.initials: P
authors.lastname: Stammet
authors.affiliation: Department of Intensive Care, University Hospital of Wales, Cardiff, United Kingdom.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Wise
authors.affiliation: Department of Anesthesia and Intensive Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Hovdenes
authors.affiliation: Department of Intensive Care, Liverpool Hospital, Sydney, New South Wales, Australia.
authors.forename: Anders
authors.initials: A
authors.lastname: Åneman
authors.affiliation: Department of Intensive Care, Academic Medical Centrum, Amsterdam, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.affiliation: Laboratory of Cardiovascular Research, Luxembourg Institute of Health, Luxembourg.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
authors.affiliation: Department of Cardiology, Lund University, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.affiliation: Department of Cardiothoracic Anesthesiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Wanscher
authors.affiliation: Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Cronberg
authors.affiliation: Department of Anesthesia and Intensive Care, Lund University, Lund, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Friberg
authors.affiliation: Copenhagen Trial Unit, Centre of Clinical Intervention Research, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Department of Intensive Care, Santa Maria degli Angeli, Pordenone, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pellis
authors.affiliation: Department of Intensive Care, Leeuwarden Medical Centrum, Leeuwarden, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Kuiper
authors.affiliation: Department of Anesthesia and Intensive Care, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Nielsen
authors.affiliation: Department of Cardiology, The Heart Centre, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003128:Coma; D015897:Comorbidity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D058687:Out-of-Hospital Cardiac Arrest / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D015850:Interleukin-6
keywords: Cardiac arrest; Hypothermia; Inflammation; Interleukins; Mortality; Prognosis