Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury

Cerebral edema is seen heterogenous group of neurological disease states that mainly fall under the categories of metabolic, infectious, neoplasia, cerebrovascular, and traumatic brain injury disease states. Regardless of the driving force, cerebral edema is defined as the accumulation of fluid in the brain's intracellular and extracellular spaces. This occurs secondary to alterations in the complex interplay between four distinct fluid compartments within the cranium. In any human cranium; fluid is contained in the blood, the cerebrospinal fluid, interstitial fluid of the brain parenchyma, and the intracellular fluid of the neurons and glia. Fluid movement occurs normally between these compartments and depends on specific concentrations of solutes (such as sodium) and water. In brain-injured states, the normal regulation of this process is disturbed and cerebral edema can develop. Cerebral edema leads to increased intracranial pressure and mortality secondary to brain tissue compression, given the confines of the fixed-volume cranium. Additionally, secondary neuronal dysfunction or death can occur at the cellular level secondary to the disruption of ion gradients that control metabolism and function.

While studies utilizing bolus dosing of hyperosmolar therapy to target signs or symptoms of increased intracranial pressure secondary to cerebral edema are numerous, there is a paucity of studies relating to continuous infusion of hyperosmolar therapy for targeted sustained hypernatremia for the prevention and treatment of cerebral edema. The investigators hypothesize that induced, sustained hypernatremia following traumatic brain injury will decrease the rate of cerebral edema formation and improve patient outcomes.


Eligibility Criteria:
Inclusion Criteria:

* Adults (18 - 60 years old)
* Severe traumatic brain injury with intracranial pressure monitoring
* Initial GCS 5-8 (obtained free of the effects of neuromuscular blockade or sedatives)
* Clearly defined time of injury no more than 8 hours before administration of study drug
* Written consent obtained from legally authorized representative (LAR)
* Severe swelling prone injury patterns:

  1. Contusion - frontal or temporal (\> 20 cc)
  2. Acute convexity subdural hematoma with any evidence of midline shift

Exclusion Criteria:

* Patients undergoing emergent (within 15 minutes) or urgent neurosurgery (within 4 hours) following emergency department arrival (bedside procedures, such as intracranial pressure monitor placement are excluded)
* Posterior fossa lesions
* Penetrating brain injury
* Spinal column instability and/or spinal cord injury with neurological deficit
* Pregnant
* Concomitant severe nonsurvivable injury
* Acute renal failure ; Chronic renal failure (serum creatinine of \> 2.5 mg/dL, history of ongoing dialysis, glomerular filtration rate \<30mL/min/1.73 m2); Severe pulmonary edema; Severe heart failure; Severe liver failure (AST, ALT, or bilirubin \> 2 times normal)
* Known use of warfarin, clopidogrel, prasugrel, cilostazol, heparin, low molecular weight heparin, heparinoids, abciximab or similar antiplatelet agents
* Treatment with another investigational drug within the prior 30 days
* Systolic blood pressure \< 90 mm HG not responsive to fluid resuscitation
* INR \> 1.4
* Hospitalization for brain injury or neurological disease within previous 3 years
* Admission serum sodium \< 135 mmol/L
* \> 8 hours from the time of injury to admission
* Fix/dilated pupil suspected to be secondary to brainstem compression
* Duret (brainstem) hemorrhage indicating brainstem herniation
* PaO2 \< 60 mmHg on admission (when blood gases are drawn as standard of care)
* Prisoner or other persons unable to make a true, voluntary and uncoerced decision whether or not to participate in the study