Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury
Condition: Brain Injuries; Craniocerebral Trauma
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Craniocerebral Trauma; Hypothermia; Wounds and Injuries
Study type: Interventional

Summary: 
      This study is a prospective multi-centre randomized trial to compare the effect of long-term
      mild hypothermia versus routine normothermic intensive management in patients with severe
      traumatic brain injury.

      The primary hypothesis is that the induction of mild hypothermia (maintained at 34-35℃) for 5
      days will improve the outcome of patients at six months post injury compared with
      normothermia.
    

Detailed description: 
      Traumatic brain injury (TBI) remains a leading cause of death and disability in people with
      injuries and constitutes a major public health concern both in developed and developing
      countries. There are multiple clinical trials of hypothermia therapy for TBI conducted,
      however, with conflicting results. Subgroup analysis of most meta-analysis showed that
      therapeutic effect was significant when hypothermia was maintained more than 48 hours. We
      have previously reported a multicenter trial of mild hypothermia (33-35℃) for severe
      traumatic brain injury, in which 215 patients was randomized to long-term mild hypothermia
      group (n = 108) for 5 ±1.3 days mild hypothermia therapy and short-term mild hypothermia
      group ( n = 107) for 2±0.6 days mild hypothermia therapy. The results shown improved outcomes
      in patients with long-term mild hypothermia and similar frequency of complications. Therefore
      we concluded that long-term hypothermia, which maintains at 33-35℃ for 5 days, could be
      considered in the management of severe traumatic brain injury.

      Hypothermia therapy was recommend as the level III evidence by the 2007 Brain Trauma
      Foundation's guideline and this treatment is currently used in our department and other large
      neurosurgical centers across China, with the aim to decrease the high intracranial pressure
      (ICP) and improve the functional outcome of TBI patients. When the decision was made, the
      injured patients would be placed on cooling blankets, tracheotomized and ventilated. The
      patients would receive continuous infusions of a paralytic drug (Tracrium 10-40 mg/hour) and
      chlorpromazine (5-10 mg/hour) administered using an infusion pump to prevent shivering. The
      dosage was given according to each patient's temperature, blood pressure, heart rate, and
      muscular tone. Once the patient's rectal temperature reached 33˚C, it was kept at
      approximately that temperature (33-35˚C) 5 to 7 days. Then the patients were passively
      rewarmed to a temperature of 37 to 38˚C at a rate no greater than 1˚C/hour, by gradual
      adjustment of the blanket thermostat.

      The present multi-center, randomized controlled trials is designed to investigate the
      efficacy and safety of long-term (5 days) mild hypothermia versus normothermia on the outcome
      of patients following severe traumatic brain injury. The primary outcome is the neurological
      function assessed at 1, 6 months post injury with the Glasgow Outcome Score (GOS).
      Additionally, the following data will also be recorded and compared: the baseline data,
      Glasgow Coma Score,imaging examination (e.g. CT scan), need of surgery, intracranial
      pressure, laboratory tests (e.g. blood routine test, liver and kidney function, blood gas
      analysis, etc), the complications (e.g. pneumonia, significant bleeding) and so on.
    

Intervention name(s): Long-term mild hypothermia; Normothermia
Intervention type(s): Other; Other
Intervention description(s): Hypothermia will be induced within 6 hours of injury and maintained at 34-35℃ for 5 days.Then the patients will be passively rewarmed to a temperature of 36 to 37˚C at a rate no greater than 0.5˚C/4 hours.; Patients assigned to the normothermia group will be kept at 36-37℃.
Other intervention name(s): Mild hypothermia therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Traumatic brain injury