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 \< 200
* 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