Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure

This study examines the role of osmotic agents in controlling brain swelling in brain injured individuals. Two osmotic agents -- mannitol and hypertonic saline -- are in common use, and they will be compared in the context of a randomized clinical trial. The goal is to determine if these agent differ in their ability to control episodes of brain swelling.

This single-center, randomized, open label trial will compare (i) 0.9% normal saline infusion and boluses of mannitol (control group) with (ii) 3% hypertonic saline, with intermittent boluses as needed, to treat elevated intracranial pressure (ICP) following severe traumatic brain injury.

Patients will be randomized to one of the two study arms following placement of an ICP monitor. Raised ICP will be defined as an ICP greater than 20 mmHG for 20 minutes or longer. In the event of such an event, the appropriate treatment will be administered.

The primary endpoint will be success in ICP control, operationalized as the proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of monitoring. Secondary endpoints include therapy intensity level, incidence of pre-determined severe adverse events, and long-term outcomes measured at 3 and 6 months post-injury.

Inclusion Criteria:

• closed traumatic brain injury
• either (i) GCS score 3-8 (inclusive), or (ii) GCS motor score of 5 or less AND abnormal admission CT scan showing intracranial pathology
• hemodynamically stable with systolic blood pressure greater than 90 mmHg
• at least 1 reactive pupil
• age between 18y and 70y (inclusive)
• INR less than 1.5

Exclusion Criteria:

• actively on hypertonic saline or mannitol
• hypernatremia (>145 meq/L)
• anuric or with creatinine greater than or equal to 2.5
• known seizure disorder
• penetrating head trauma
• suspected anoxic events
• history of, or CT confirmation of, previous brain injury
• any injury that, in the opinion of the Principal Investigator, has a high likelihood of death with the first 72 hours post-injury
• any treatment, condition, or injury that contraindicates treatment with hypertonic saline