title: Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children.
abstract: OBJECTIVE
  To determine whether moderate hypothermia (HYPO) (32-33 degrees C) begun in the early period after severe traumatic brain injury (TBI) and maintained for 48 hours is safe compared with normothermia (NORM) (36.5-37.5 degrees C).
  
  
  METHODS
  After severe (Glasgow Coma Scale score < or =8) nonpenetrating TBI, 48 children less than 13 years of age admitted within 6 hours of injury were randomized after stratification by age to moderate HYPO (32-33 degrees C) treatment in conjunction with standardized head injury management versus NORM in a multicenter trial. An additional 27 patients were entered into a parallel single-institution trial of excluded patients because of late transfer or consent (delayed in transfer >6 h but within 24 h of admission), unknown time of injury (e.g., child abuse), and adolescence (e.g., aged 13-18 yr). Assessments of safety included mortality, infection, coagulopathy, arrhythmias, and hemorrhage as well as ability to maintain target temperature, mean intracranial pressure (ICP), and percent time of ICP less than 20 mm Hg during the cooling and subsequent rewarming phases. Additionally, assessments of neurocognitive outcomes were obtained at 3 and 6 months of follow-up.
  
  
  RESULTS
  Moderate HYPO after severe TBI in children was found to be safe relative to standard management and NORM in children of all ages and in children with delay of initiation of treatment up to 24 hours. Although there was decreased mortality in HYPO in both studies, there was an increased potential for arrhythmias with HYPO, although they were manageable with fluid administration or rewarming. Additionally, there was a reduction in mean ICP during the first 72 hours after injury in both studies, although rebound ICP elevations in HYPO compared with those in NORM were noted for up to 10 to 12 hours after rewarming. Although functional outcome at 3 or 6 months did not differ between treatment groups, functional outcome tended to improve from the 3- to 6-month cognitive assessment in HYPO compared with NORM, although the sample size was too small for any definitive conclusions.
  
  
  CONCLUSIONS
  HYPO is likely a safe therapeutic intervention for children after severe TBI up to 24 hours after injury. Further studies are necessary and warranted to determine its effect on functional outcome and intracranial hypertension.
authors.affiliation: Department of Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. david.adelson@chp.edu
authors.forename: P David
authors.initials: PD
authors.lastname: Adelson
authors.forename: John
authors.initials: J
authors.lastname: Ragheb
authors.forename: Paul
authors.initials: P
authors.lastname: Kanev
authors.forename: Douglas
authors.initials: D
authors.lastname: Brockmeyer
authors.forename: Sue R
authors.initials: SR
authors.lastname: Beers
authors.forename: S Danielle
authors.initials: SD
authors.lastname: Brown
authors.forename: Laura D
authors.initials: LD
authors.lastname: Cassidy
authors.forename: Yuefang
authors.initials: Y
authors.lastname: Chang
authors.forename: Harvey
authors.initials: H
authors.lastname: Levin
mesh_terms: D000293:Adolescent; D001930:Brain Injuries / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D019586:Intracranial Hypertension / Q000628:therapy; D018579:Patient Selection; D012449:Safety; D016896:Treatment Outcome