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

Traumatic Brain Injury research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Traumatic Brain Injury

Subdural Hematoma

Cerebral Contusion

Head Injury

Cerebral Edema

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Induced, sustained hypernatremia using hypertonic salinePatients 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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Standard CarePatients will be managed to maintain a goal serum sodium of > 135 mmol/L , a well recognized value in the management of severe traumatic brain injury.

Induced HypernatremiaPatients will be treated with induced, sustained hypernatremia for 5 days following injury by using hypertonic saline to target a goal serum sodium of 150-160 mmol/L

Study Status

Withdrawn

Start Date: July 2012

Completed Date: August 2013

Phase: Phase 1/Phase 2

Type: Interventional

Design:

Primary Outcome: Primary Efficacy Objective

Secondary Outcome: Short term neurological outcome

Study sponsors, principal investigator, and references

Principal Investigator: Brian P Walcott, MD

Lead Sponsor: Massachusetts General Hospital

Collaborator:

More information:https://clinicaltrials.gov/show/NCT01605357

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