title: Impact of time to return of spontaneous circulation on neuroprotective effect of targeted temperature management at 33 or 36 degrees in comatose survivors of out-of hospital cardiac arrest.
abstract: OBJECTIVE
  Time to Return of Spontaneous Circulation (ROSC) has a plausible relation to severity of hypoxic injury before and during resuscitation in Out-of-Hospital Cardiac Arrest (OHCA), and has consistently been associated with adverse outcome. The effect of Targeted Temperature Management (TTM) may not be similar over the full spectrum of time to ROSC. This study investigated the possible beneficial effect of targeting 33°C over 36°C on the prognostic importance of time to ROSC.
  
  
  METHODS
  In predefined sub-study of the TTM-trial (NEJM 2013) we investigated the relationship between time to ROSC, level of TTM and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) scale and modified Rankin Scale (mRS) after 180 days.
  
  
  RESULTS
  Prolonged time to ROSC was significantly associated with increased mortality with a hazard ratio (HR) of 1.02 per minute (95% CI 1.01-1.02). Level of TTM did not modify the association of time to ROSC and mortality, pinteraction=0.85. Prolonged time to ROSC was associated with reduced odds of surviving with a favorable neurological outcome for CPC (p=0.008 for CPC 1-2) and mRS (p=0.17, mRS 0-3) with no significant interaction with level of TTM.
  
  
  CONCLUSIONS
  Time to ROSC remains a significant prognostic factor in comatose OHCA patients with regards to risk of death and risk of adverse neurological outcome. For any time to ROSC, targeting 33°C in TTM was not associated with benefit with regards to reducing mortality or risk of adverse neurological outcome compared to targeting 36°C.
authors.affiliation: Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: Jesper.kjaergaard.05@regionh.dk.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
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 B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Matilde
authors.initials: M
authors.lastname: Winther-Jensen
authors.affiliation: Department of Cardiothoracic Anesthesiology RT, The Heart Centre, Copenhagen University Hospital, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Wanscher
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 Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hartvig Thomsen
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 Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Cronberg
authors.affiliation: Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Bro-Jeppesen
authors.affiliation: Department of Cardiology, Skåne University Hospital, Lund, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.affiliation: Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Friberg
authors.affiliation: Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Søholm
authors.affiliation: Department of Intensive Care, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Gasche
authors.affiliation: Department of Intensive Care, Academic Medical Centrum, Amsterdam, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
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 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 Intensive Care, Liverpool hospital, Sydney, New South Wales, Australia.
authors.forename: Anders
authors.initials: A
authors.lastname: Åneman
authors.affiliation: Department of Cardiology B, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
mesh_terms: D000368:Aged; D001831:Body Temperature / Q000502:physiology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003128:Coma / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function / Q000502:physiology*; D012189:Retrospective Studies; D017741:Survivors / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome