NCT01605357

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

A Randomized, Open Label Clinical Trial of Sustained Hypernatremia for the Prevention and Treatment of Cerebral Edema in Traumatic Brain Injury

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Traumatic Brain Injury
• Subdural Hematoma
• Cerebral Contusion
• Head Injury
• Cerebral Edema

Interventions

Type	Name	Description
DRUG	Induced, sustained hypernatremia using hypertonic saline	Patients in the experimental arm will receive hypertonic saline to target a serum sodium goal of 150 - 160 mmol/L. All hypertonic saline will be administered intravenously. Loading phase: Upon enrollment 23.4 % hypertonic saline (volume 20 cc) will be administered via a central venous catheter. A continuous infusion of 3% hypertonic saline will be administered at a rate of 30 cc per hour and titrated every six hours to target a serum sodium goal of 150-160 mmol/L. Maintenance phase: Titrate serum sodium to 150-160 mmol/L using continuous 3% hypertonic saline infusion. Discontinuation phase: After 5 days of completed therapy, begin to wean 3% hypertonic saline rate by 10cc every 6 hours. Discontinue hypertonic saline infusion after infusing at a rate of 20cc an hour for 6 hours. Bolus dosing of hypertonic saline and mannitol are to be administered at the discretion of the provider to treat elevated intracranial pressure based on practice guidelines
DRUG	Standard of care (hypertonic saline and mannitol; serum sodium)	Bolus dosing of hypertonic saline and mannitol are to be administered at the discretion of the provider to treat elevated intracranial pressure based on practice guidelines. Hyponatremia ( serum sodium \< 135 mmol/L) is to be corrected at the discretion of the provider.

Timeline

• Start date: 2012-07-01
• Primary completion: 2013-07-01
• Completion: 2013-08-01
• First posted: 2012-05-24
• Last updated: 2016-12-12