Hypothermia therapy after traumatic brain injury in children

N Engl J Med. 2008 Jun 5;358(23):2447-56. doi: 10.1056/NEJMoa0706930.


Background: Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown.

Methods: In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months.

Results: A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups.

Conclusions: In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Body Temperature
  • Brain Injuries / classification
  • Brain Injuries / complications
  • Brain Injuries / mortality
  • Brain Injuries / therapy*
  • Child
  • Child, Preschool
  • Disabled Children
  • Female
  • Glasgow Coma Scale
  • Humans
  • Hypotension / drug therapy
  • Hypothermia, Induced* / adverse effects
  • Infant
  • Intracranial Pressure / drug effects
  • Kaplan-Meier Estimate
  • Length of Stay
  • Male
  • Persistent Vegetative State / etiology
  • Rewarming
  • Saline Solution, Hypertonic / administration & dosage
  • Statistics, Nonparametric
  • Time Factors
  • Treatment Failure
  • Vasoconstrictor Agents / therapeutic use


  • Saline Solution, Hypertonic
  • Vasoconstrictor Agents

Associated data

  • ISRCTN/ISRCTN77393684