Study of the Safety and Efficacy of Conivaptan (Vaprisol®) to Raise Serum Sodium Levels in Patients With Severe Traumatic Brain Injury

• Safety profile: number of events of increased serum sodium levels above the intended target range, and any adverse events occurring during the study period. [ Time Frame: Hospital Stay ] [ Designated as safety issue: Yes ]
• 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 [ Time Frame: Until 48 hours post randomization ] [ Designated as safety issue: No ]
• Serum sodium stability: a. Stable state of hypernatremia b. Sodium variability c. Time to achievement of target sodium levels after randomization [ Time Frame: Until 48 hours post randomization ] [ Designated as safety issue: Yes ]
• Fluid balance [ Time Frame: Until 48 hours post randomization ] [ Designated as safety issue: No ]
• Cerebral edema: a. Mean ICP in the first 48 hours after randomization b. Reduction of cerebral edema [ Time Frame: Until 48 hours post randomization ] [ Designated as safety issue: Yes ]

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.

• Experimental: Conivaptan (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.
  Intervention: Drug: Conivaptan (Vaprisol)
• No Intervention: Standard Care
  No intervention

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.