Hypertonic Saline With Dextran for Treating Hypovolemic Shock and Severe Brain Injury

BACKGROUND:

Trauma is the leading cause of death among Americans between the ages of 1 and 35 years. The
majority of these deaths result from hypovolemic shock, a type of shock in which the heart
is unable to supply enough blood to the body, and the resulting severe brain injury.
Patients in hypovolemic shock develop a state of systemic tissue ischemia with a subsequent
reperfusion injury at the time of fluid resuscitation. Conventional resuscitation of these
patients involves the intravenous administration of a large volume of isotonic or slightly
hypotonic (lactated ringers) solutions beginning in the pre-hospital environment. Previous
studies have suggested that an alternative resuscitation fluid, HSD, may reduce mortality in
these patients; but these studies have not been conclusive. Furthermore, HSD may have
specific advantages in the brain-injured patient, as it may aid in the rapid restoration of
cerebral perfusion, prevent extravascular fluid sequestration, and thus, limit secondary
brain injury. In addition, recent studies have demonstrated that hypertonicity significantly
alters the activation of inflammatory cells, which may result in a reduction in subsequent
organ injury following whole body ischemia/reperfusion and ultimately decrease nosocomial
infection rates.

Blunt trauma victims with low blood pressures will be identified by pre-hospital providers
(paramedics and flight nurses) and randomized to receive either 250 cc of HSD or 250 cc of
isotonic solution (lactated ringer's solution). Lactated ringer's solution is the current
standard of care with which the ambulances and helicopters will be supplied. All bags of
study solution will be prepared by the Harborview Medical Center pharmacy.

DESIGN NARRATIVE:

This randomized clinical trial seeks to evaluate the clinical outcome and inflammatory cell
function of patients in shock following blunt traumatic injury who are randomized to receive
either 7.5% hypertonic saline/6% dextran (HSD) followed by lactated ringer's solution or
lactated ringer's solution alone. It is hypothesized that HSD resuscitation will inhibit the
initial excessive systemic activation of the inflammatory response, which will translate
into a reduction in the incidence of organ dysfunction typically induced by this response.
Furthermore, the study will evaluate the impact of HSD resuscitation on recovery following
traumatic brain injury, as previous studies suggest that this subgroup has the greatest
survival advantage from HSD intervention. The specific aims for this study include the
following: Aim 1: To determine the impact of pre-hospital administration of HSD on the
development of organ failure following blunt traumatic injury with hypovolemic shock. Aim 2:
To determine the impact of pre-hospital administration of HSD on the neurologic outcome
following brain injury for patients in hypovolemic shock. Aim 3a: To determine the effect of
pre-hospital administration of HSD on the activation of circulating neutrophils and
monocytes. Aim 3b: To determine the effect of pre-hospital administration of HSD on the
activation of T lymphocytes. The study builds upon previous research that has demonstrated
the safety and practicality of this resuscitation strategy in the pre-hospital environment.
A more detailed understanding of the immuno-inflammatory effects of hypertonicity for all
patients and the long-term neurologic outcome for patients with brain injury is critical for
determining the role of this resuscitation approach in such critically injured patients.

Inclusion Criteria:

- Recent blunt trauma

- Of adult size if age is unknown

- Pre-hospital systolic bloood pressure 90 mm Hg or less

- Altered mental status

- Transported directly to Harborview Medical Center from the injury event

Exclusion Criteria:

- Ongoing CPR

- Transferred from outside hospitals

- Pregnant or suspected pregnancy

- Presence of injuries from penetrating trauma

- Receiving more than 2000 cc of crystaloid prior to study fluid administration