Comparison Between Different Types of Oxygen Treatment Following Traumatic Brain Injury

Brain injury continues to be a major cause of death and disability throughout the world. Our
investigations of hyperbaric oxygen treatment (HBOT) indicate that it is a relatively safe
treatment that has promise as a potential therapy for patients with severe traumatic brain
injury (TBI). The goals of the present proposal are to further elucidate the mechanisms of
action of HBOT on severe TBI and to test hypotheses that are crucial to the possible future
design of a Phase III clinical trial.

Our initial prospective clinical trial to assess the effectiveness of HBOT in severe TBI
documented very significant improvement in survival, particularly in certain subgroups of
patients. In our second study, HBOT was found to improve cerebral aerobic metabolism in
patients with severe TBI, reduce elevated intracranial pressure, and had a persistent
positive effect for at least six hours following the treatment. Our work suggests that HBOT
allows the brain to utilize increased amounts of oxygen more efficiently following
treatment.

Recently, increasing the inspired oxygen concentration (FiO2) to 100% has been proposed as
an alternative way of delivering supranormal levels of oxygen to severe TBI patients.
Experimental investigation in the fluid percussion rat model using HBOT at 1.5 ATA
(atmospheres absolute) for 60 minutes followed by 3 hours of 100%fraction of inspired oxygen
(FiO2) have given optimum results in terms of mitochondrial functional and neurobehavioral
improvement.

The clinical and experimental data together provide a strong basis for the restorative
effect of the combination of hyper- and normobaric hyperoxia on severe TBI. The goal of this
study is to evaluate the use of HBOT and 100% FiO2 separately and in combination.

Inclusion Criteria:

- All closed head trauma victims with GCS score < 8, when no effects from paralytics,
sedation, alcohol and/or street drugs are present.

- Informed consent obtained.

- Entry into the study within 24 hours after injury.

- If a patient enters the hospital with a mild or moderate brain injury and
subsequently deteriorates to a GCS < 8 within 48 hours of admission, the patient is
considered a candidate for entry into the study.

- CT scan score > II in accordance with the classification system of the Traumatic Coma
Data Bank.

Exclusion Criteria:

- Consent could not be obtained.

- Patients who are brain dead or close to brain death (fixed, dilated pupils).

- Unstable pulmonary status requiring FiO2 of 50% or greater to maintain a PaO2 of 70
mm Hg or greater.

- History of severe pulmonary disease, such as COPD or asthma.

- Unstable fracture (spine, pelvis, femur, etc) preventing placement into the HBO
chamber.

- Patients placed in barbiturate coma during initial management due to the potential
effect barbiturates have on cerebral metabolism.

- Age range < 16 years or > 65 years.

- Coagulopathy.

- Pregnancy.

- Severe mental retardation or prior severe head injury.

- High velocity penetrating injury to the head,(e.g. gunshot wound).

- Multiple organ failure.

- Massive cerebral hemisphere or brainstem hematoma, stroke