title: Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest.
abstract: OBJECTIVE
  Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated. The aim of the study was to assess the prognostic implication of PHF in a large consecutive cohort of comatose survivors after out-of-hospital cardiac arrest (OHCA) treated with TH.
  
  
  METHODS
  In the period 2004-2010, a total of 270 patients resuscitated after OHCA and surviving a 24-h protocol of TH with a target temperature of 32-34°C were included. The population was stratified in two groups by median peak temperature (≥38.5°C) within 36h after rewarming: PHF and no-PHF. Primary endpoint was 30-days mortality and secondary endpoint was neurological outcome assessed by Cerebral Performance Category (CPC) at hospital discharge.
  
  
  RESULTS
  PHF (≥38.5°C) was associated with a 36% 30-days mortality rate compared to 22% in patients without PHF, plog-rank=0.02, corresponding to an adjusted hazard rate (HR) of 1.8 (95% CI: 1.1-2.7), p=0.02). The maximum temperature (HR=2.0 per °C above 36.5°C (95% CI: 1.4-3.0), p=0.0005) and the duration of PHF (HR=1.6 per 8h (95% CI: 1.3-2.0), p<0.0001) were also independent predictors of 30-days mortality in multivariable models. Good neurological outcome (CPC1-2) versus unfavourable outcome (CPC3-5) at hospital discharge was found in 61% vs. 39% in the PHF group compared to 75% vs. 25% in the No PHF group, p=0.02.
  
  
  CONCLUSIONS
  Post-hypothermia fever ≥38.5°C is associated with increased 30-days mortality, even after controlling for potential confounding factors. Avoidance of PHF as a therapeutic target should be evaluated in prospective randomized trials.
authors.affiliation: Department of Cardiology, The Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: jbj@dadlnet.dk.
authors.forename: John
authors.initials: J
authors.lastname: Bro-Jeppesen
authors.forename: Christian
authors.initials: C
authors.lastname: Hassager
authors.forename: Michael
authors.initials: M
authors.lastname: Wanscher
authors.forename: Helle
authors.initials: H
authors.lastname: Søholm
authors.forename: Jakob H
authors.initials: JH
authors.lastname: Thomsen
authors.forename: Freddy K
authors.initials: FK
authors.lastname: Lippert
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Møller
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaergaard
mesh_terms: D001925:Brain Damage, Chronic / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology* / Q000401:mortality*; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000401:mortality* / Q000628:therapy*; D011379:Prognosis; D012985:Software Design; D016896:Treatment Outcome
keywords: Fever; Mortality; Neurological outcome; Out-of-hospital cardiac arrest; Therapeutic hypothermia