title: Comparison of hypothermia and normothermia after severe traumatic brain injury in children (Cool Kids): a phase 3, randomised controlled trial.
abstract: BACKGROUND
  On the basis of mixed results from previous trials, we assessed whether therapeutic hypothermia for 48-72 h with slow rewarming improved mortality in children after brain injury.
  
  
  METHODS
  In this phase 3, multicenter, multinational, randomised controlled trial, we included patients with severe traumatic brain injury who were younger than 18 years and could be enrolled within 6 h of injury. We used a computer-generated randomisation sequence to randomly allocate patients (1:1; stratified by site and age [<6 years, 6-15 years, 16-17 years]) to either hypothermia (rapidly cooled to 32-33°C for 48-72 h, then rewarmed by 0·5-1·0°C every 12-24 h) or normothermia (maintained at 36·5-37·5°C). The primary outcome was mortality at 3 months, assessed by intention-to-treat analysis; secondary outcomes were global function at 3 months after injury using the Glasgow outcome scale (GOS) and the GOS-extended pediatrics, and the occurrence of serious adverse events. Investigators assessing outcomes were masked to treatment. This trial is registered with ClinicalTrials.gov, number NCT00222742.
  
  
  RESULTS
  The study was terminated early for futility after an interim data analysis on data for 77 patients (enrolled between Nov 1, 2007, and Feb 28, 2011): 39 in the hypothermia group and 38 in the normothermia group. We detected no between-group difference in mortality 3 months after injury (6 [15%] of 39 patients in the hypothermia group vs two [5%] of 38 patients in the normothermia group; p=0·15). Poor outcomes did not differ between groups (in the hypothermia group, 16 [42%] patients had a poor outcome by GOS and 18 [47%] had a poor outcome by GOS-extended paediatrics; in the normothermia group, 16 [42%] patients had a poor outcome by GOS and 19 [51%] of 37 patients had a poor outcome by GOS-extended paediatrics). We recorded no between-group differences in the occurrence of adverse events or serious adverse events.
  
  
  CONCLUSIONS
  Hypothermia for 48 h with slow rewarming does not reduce mortality of improve global functional outcome after paediatric severe traumatic brain injury.
  
  
  BACKGROUND
  National Institute of Neurological Disorders and Stroke and National Institutes of Health.
authors.affiliation: Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ 85016, USA. dadelson@phoenixchildrens.com
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Wisniewski
authors.forename: John
authors.initials: J
authors.lastname: Beca
authors.forename: S Danielle
authors.initials: SD
authors.lastname: Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Bell
authors.forename: J Paul
authors.initials: JP
authors.lastname: Muizelaar
authors.forename: Pamela
authors.initials: P
authors.lastname: Okada
authors.forename: Sue R
authors.initials: SR
authors.lastname: Beers
authors.forename: Goundappa K
authors.initials: GK
authors.lastname: Balasubramani
authors.forename: Deborah
authors.initials: D
authors.lastname: Hirtz
mesh_terms: D000293:Adolescent; D001831:Body Temperature / Q000502:physiology; D001930:Brain Injuries / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods* / Q000401:mortality*; D008297:Male; D012720:Severity of Illness Index; D013997:Time Factors