Brain Oxygen Optimization in Severe TBI, Phase 3

Inclusion Criteria: * Non-penetrating traumatic brain injury * Glasgow Coma Scale (GCS) 3-8 measured off paralytics * Glasgow Coma Scale motor score \< 6 if endotracheally intubated * Evidence of intracranial trauma on CT scan * Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital * Able to place intracranial probes and randomize within 12 hours from injury * Age greater than or equal to 14 years Exclusion Criteria: * Non-survivable injury * Bilaterally absent pupillary response in the absence of paralytic medication * Contraindication to the placement of intracranial probes * Treatment of brain tissue oxygen values prior to randomization * Planned use of devices which may unblind treating physicians to brain tissue hypoxia * Systemic sepsis at screening * Refractory hypotension * Refractory systemic hypoxia * PaO2/FiO2 ratio \< 150 * Known pre-existing neurologic disease with confounding residual neurological deficits * Known inability to perform activities of daily living (ADL) without assistance prior to injury * Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments * Pregnancy * Prisoner * On EFIC Opt-Out list as indicated by a bracelet or medical alert