Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury
Randomized Controlled Trial of Long-term Mild Hypothermia for Severe Traumatic Brain Injury
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.
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.
Inclusion Criteria:

 -  Age 18 - 65 years within 6 hours post injury;

 -  Closed head injury;

 -  Glasgow Coma Scale(GCS) score 4 to 8 after resuscitation;

 -  The intracranial pressure is more than 25 mmHg;

 -  Cerebral contusion on computed tomographic scan.

 Exclusion Criteria:

 -  GCS of 3 with bilateral fixed and dilated pupils;

 -  A life-threatening injury to an organ other than the brain;

 -  No spontaneous breathing or cardiac arrest at the scene of the injury;

 -  No consent;

 -  Pregnancy.