Hypertonic Resuscitation Following Severe Traumatic Brain Injury (TBI)

University of Washington

Status and phase: Terminated; Phase 3

Conditions: Brain Injuries, Traumatic

Treatments: Drug: 7.5% Hypertonic Saline (HS); Drug: 0.9% Normal Saline (NS); Drug: 7.5% Hypertonic Saline in 6% Dextran-70 (HSD)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; NIH

Identifiers

NCT00316004

28226-A - IND 12505

IND #12505 TBI cohort (Other Identifier)

5U01HL077863-05 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this study is to determine if hypertonic saline with and without dextran can improve neurologic outcomes in victims of severe traumatic brain injury (TBI).

Injury and lost blood from trauma can cause your body to go into shock (low blood pressure related to blood loss). This decreased blood flow can lead to organ damage. In order to restore the blood pressure and blood flow, the medics give fluids into the patients' veins as soon as possible. This is called "resuscitation". The fluid most commonly used is "isotonic" or one that is the same salt concentration as the blood. The investigators are trying to determine if infusing a "hypertonic" fluid or one more concentrated than the blood can increase the blood pressure and restore blood flow more efficiently. The hypertonic fluids they are using are called hypertonic saline with dextran (HSD) and hypertonic saline (no dextran). Hypertonic saline is a salt solution that is slightly more concentrated than blood. Dextran is a sugar solution.

Full description

To determine if prehospital administration of 7.5% Hypertonic Saline in 6% Dextran-70 (HSD) OR 7.5% Hypertonic Saline (HS) compared to current standard therapy with NS as an initial resuscitation fluid affects neurological outcome following severe traumatic brain injury.

Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the pre-hospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these patients. Furthermore, hypertonic fluids may have specific advantages in the brain-injured patient, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection.

This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with severe TBI as manifested by a pre-hospital GCS of 8 or less. Patients will be randomized to a single 250cc IV dose of 7.5% saline in 6% Dextran-70 (HSD), 7.5% saline (HS) or normal saline as the initial fluid for pre-hospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days. Patients will have neurologic outcome measurements at discharge, 1 month post discharge, and 6 months post injury. Enrollment will be restricted to age ≥ 15 years or ≥ 50 kg if age is unknown.

Enrollment: 1,331 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Blunt trauma

• Pre-hospital Glasgow Coma Scale equal to or less than 8(GCS≤8)*

• Age 15 years or older or 50 kg or more

  • Patients who met the inclusion criteria above and did not meet the exclusion criteria below but who had systolic blood pressure (SBP) ≤70 or SBP>70 and SBP≤90 and heart rate (HR)≥108 were included in the Hypertonic Resuscitation following Traumatic Injury study that focused on shock patients who may or may not have a traumatic brain injury (TBI). In other words, patients with both TBI and shock would not be included in this study of TBI patients without shock at the time of enrollment.

Exclusion criteria

• Known or suspected pregnancy
• Age younger than 15 years or less than 50 kg if age unknown
• Ongoing pre-hospital cardiopulmonary resuscitation (CPR)
• Administration of more than 2L crystalloid or any colloid or blood products
• Severe hypothermia (T less than 28C)
• Drowning or asphyxia due to hanging
• Burns TBSA more than 20%
• Isolated penetrating injury to the head
• Inability to obtain pre-hospital intravenous access
• Time of call received at dispatch to study intervention more than four hours
• Known prisoners

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,331 participants in 3 patient groups, including a placebo group

7.5% hypertonic saline/6% dextran (HSD)

Experimental group

Description:

250 ml intravenous bolus administration of 7.5% saline/6% dextran 70

Treatment:

Drug: 7.5% Hypertonic Saline in 6% Dextran-70 (HSD)

7.5% hypertonic saline (HS)

Experimental group

Description:

250 ml intravenous bolus administration of 7.5% hypertonic saline

Treatment:

Drug: 7.5% Hypertonic Saline (HS)

0.9% normal saline (NS)

Placebo Comparator group

Description:

250 ml intravenous bolus administration of 0.9% saline

Treatment:

Drug: 0.9% Normal Saline (NS)