Severe Traumatic Brain Injury
Conditions
Keywords
Traumatic Brain Injury, Conivaptan, Vaprisol, Sodium
Brief summary
The investigators plan to utilize conivaptan (Vaprisol) to promote isolated water loss, in combination with normal (physiologic) fluid replacement to maintain a normal blood volume status, in patients with severe TBI. The goal of this therapy is to raise blood sodium in a controlled fashion in subjects with severe TBI, and reduce the use of hypertonic saline infusion. We hypothesize that this therapy will maintain a stable state of high blood sodium, while decreasing the overall sodium load needed to achieve these goals.
Interventions
DRUGConivaptan (Vaprisol)
Conivaptan (Vaprisol) will be administered in a single dose of 20 mg, mixed with 100 mL of 5% dextrose in water, and delivered over 30 minutes.
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years old or greater * Initial diagnosis of an isolated, severe traumatic brain injury (Glasgow Coma Score of 8 or less upon initial evaluation) * Cerebral edema with a head CT and Marshall classification of diffuse injury type II, III, or IV. * Primary care team orders to raise blood sodium by 10 mEq/L from baseline. * Placement of an intraparenchymal fiberoptic monitor to monitor intracranial pressure (ICP).
Exclusion criteria
* Age \< 18 years * Signs of hypovolemia including systolic BP \< 90 mmHg * Signs of liver disease including jaundice and ascites * AST \> 35 units/L * ALT \> 35 units/L * Signs of renal disease including history of dialysis * Serum creatinine \> 1.5 mg/dL * BUN \> 20 mg/dL range * Baseline serum sodium \>/= 145 mEq/L * Pregnant or lactating females * Concomitant use of digoxin, ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, simvastatin and lovastatin * Presentation to the tertiary care hospital \> 24 hours post-injury * Multi-system traumatic injuries * Diabetes Insipidus * Anticipation of diagnosis compatible with brain death, or no expectation of survival with 48 hours.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of events of excessive rate of increase in sodium levels (>1 mEq/hr). | Every 4 hours |
Secondary
| Measure | Time frame |
|---|---|
| Safety profile: number of events of increased serum sodium levels above the intended target range, and any adverse events occurring during the study period. | Hospital Stay |
| Sodium load: Sodium load is defined as the cumulative amount of sodium administered by enteral and parenteral routes from the time of randomization to 48 hours post-randomization | Until 48 hours post randomization |
| Serum sodium stability: a. Stable state of hypernatremia b. Sodium variability c. Time to achievement of target sodium levels after randomization | Until 48 hours post randomization |
| Fluid balance | Until 48 hours post randomization |
| Cerebral edema: a. Mean ICP in the first 48 hours after randomization b. Reduction of cerebral edema | Until 48 hours post randomization |
Countries
United States
Outcome results
None listed