The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury
Condition: Brain Injuries, Traumatic
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Hypothermia; Wounds and Injuries
Study type: Interventional

Summary: 
      Traumatic brain injury (TBI) is a leading cause of death and long term disability,
      particularly in young adults. Studies from Australia have shown that approximately half of
      those with severe traumatic brain injury will be severely disabled or dead 6 months post
      injury. Given the young age of many patients with severe TBI and the long term prevalence of
      major disability, the economic and more importantly the social cost to the community is very
      high.

      Pre-hospital and hospital management of patients with severe brain injury focuses on
      prevention of additional injury due primarily to lack of oxygen and insufficient blood
      pressure. This includes optimising sedation and ventilation, maintaining the fluid balance
      and draining Cerebrospinal Fluid (CSF) and performing surgery where appropriate. In recent
      years there has been a research focus on specific pharmacologic interventions, however, to
      date, there has been no treatment that has been associated with improvement of neurological
      outcomes.

      One treatment that shows promise is the application of hypothermia (cooling). This treatment
      is commonly used in Australia to decrease brain injury in patients with brain injury
      following out-of-hospital cardiac arrest. Cooling is thought to protect the brain using a
      number of mechanisms. There have been a number of animal studies that have looked at how
      cooling is protective and also some clinical research that suggests some benefit. However at
      the current time there is insufficient evidence to provide enough proof that cooling should
      be used routinely for patients with brain injury and like all treatments there can be some
      risks and side effects.

      The POLAR trial has been developed to investigate whether early cooling of patients with
      severe traumatic brain injury is associated with better outcomes. It is a randomised
      controlled trial, which is a type of trial that provides the highest quality of evidence.

      The null hypothesis is that there is no difference in the proportion of favourable
      neurological outcomes six months after severe traumatic brain injury in patients treated with
      early and sustained hypothermia, compared to standard normothermic management.
    

Detailed description: 
      Eligible patients will be randomised in the pre-hospital setting or on admission to the
      Emergency Department. POLAR study trained paramedics and physicians will screen patients in
      the pre-hospital setting. Eligible patients will be randomised if they fulfil the inclusion
      criteria with no pre-hospital exclusion criteria. Those randomised to the normothermia group
      will follow standard care. For those randomised to the "cooling arm", pre-hospital
      prophylactic hypothermia will be induced by exposure and by infusing up to 2 litres
      intravenous cold (4°C) 0.9% sodium chloride aiming for a core temperature of 35°C during
      transport. In the emergency department the "cooling arm" patients will be assessed to exclude
      significant bleeding and, once significant bleeding has been excluded, surface cooling
      vests/wraps will be applied to reach the target core temperature of 33°C. The patient will be
      then maintained at this temperature for a further 72 hours. Patients with significant
      bleeding will have cooling withheld until it is safe to decrease the temperature to the
      target core temperature of 33°C. Patients who have not been randomised pre-hospital will be
      re-screened in the ED. Eligible patients will be randomised if they fulfil the inclusion
      criteria with no ED exclusion criteria. Hypothermia will be induced by administration of up
      to 2L intravenous ice-cold (4°C) 0.9% sodium chloride followed by application of the surface
      cooling vests/wraps to achieve the target core temperature of 33°C. Patients allocated to
      standard 'normothermic' care will be maintained at a core temperature of 37°C ± 0.5°C.
    

Intervention name(s): Hypothermia
Intervention type(s): Other
Intervention description(s): exposure: Early and sustained hypothermia. Hypothermia will initially be induced by infusion of up to 2L ice cold saline. Following a safety assessment the patient will be rapidly cooled to 33C using surface temperature control equipment. They will be maintained at 33C for 72 hours. Rewarming will occur at a rate of 1C/4hrs and will be titrated to intracranial pressure (ICP) control and BP.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: trauma; Brain injury; Pre-hospital; cooling