title: Early induction of hypothermia for evacuated intracranial hematomas: a post hoc analysis of two clinical trials.
abstract: OBJECTIVE
  The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes.
  
  
  METHODS
  The National Acute Brain Injury Study: Hypothermia I (NABIS:H I) was a randomized multicenter clinical trial of 392 patients with severe brain injury treated using normothermia or hypothermia for 48 hours with patients reaching 33°C at 8.4 ± 3 hours after injury. The National Acute Brain Injury Study: Hypothermia II (NABIS:H II) was a randomized, multicenter clinical trial of 97 patients with severe brain injury treated with normothermia or hypothermia for 48 hours with patients reaching 35°C within 2.6 ± 1.2 hours and 33°C within 4.4 ± 1.5 hours of injury. Entry and exclusion criteria, management, and outcome measures in the 2 trials were similar.
  
  
  RESULTS
  In NABIS:H II among the patients with evacuated intracranial hematomas, outcome was poor (severe disability, vegetative state, or death) in 5 of 15 patients in the hypothermia group and in 9 of 13 patients in the normothermia group (relative risk 0.44, 95% CI 0.22-0.88; p = 0.02). All patients randomized to hypothermia reached 35°C within 1.5 hours after surgery start and 33°C within 5.55 hours. Applying these criteria to NABIS:H I, 31 of 54 hypothermia-treated patients reached a temperature of 35°C or lower within 1.5 hours after surgery start time, and the remaining 23 patients reached 35°C at later time points. Outcome was poor in 14 (45%) of 31 patients reaching 35°C within 1.5 hours of surgery, in 14 (61%) of 23 patients reaching 35°C more than 1.5 hours of surgery, and in 35 (60%) of 58 patients in the normothermia group (relative risk 0.74, 95%, CI 0.49-1.13; p = 0.16). A meta-analysis of 46 patients with hematomas in both trials who reached 35°C within 1.5 hours of surgery start showed a significantly reduced rate of poor outcomes (41%) compared with 94 patients treated with hypothermia who did not reach 35°C within that time and patients treated at normothermia (62%, p = 0.009).
  
  
  CONCLUSIONS
  Induction of hypothermia to 35°C before or soon after craniotomy with maintenance at 33°C for 48 hours thereafter may improve outcome of patients with hematomas and severe traumatic brain injury. Clinical trial registration no.: NCT00178711.
authors: Vivian L. Smith Center for Neurologic Research, Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, TX, USA. guy@guyclifton.com
authors: Guy L
authors: GL
authors: Clifton
authors: Christopher S
authors: CS
authors: Coffey
authors: Sierra
authors: S
authors: Fourwinds
authors: David
authors: D
authors: Zygun
authors: Alex
authors: A
authors: Valadka
authors: Kenneth R
authors: KR
authors: Smith
authors: Melisa L
authors: ML
authors: Frisby
authors: Richard D
authors: RD
authors: Bucholz
authors: Elisabeth A
authors: EA
authors: Wilde
authors: Harvey S
authors: HS
authors: Levin
authors: David O
authors: DO
authors: Okonkwo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology*; D003399:Craniotomy / Q000379:methods; D015600:Glasgow Coma Scale; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D020198:Intracranial Hemorrhage, Traumatic / Q000503:physiopathology* / Q000601:surgery*; D007427:Intracranial Pressure / Q000502:physiology; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D015427:Reperfusion Injury / Q000517:prevention & control*; D013396:Suction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult