Hypertonic Modulation of Inflammation Following Injury

This project seeks to determine the effect of prehospital resuscitation with hypertonic saline vs. conventional crystalloids on the inflammatory response after injury. The leading cause of late mortality following injury is multiple organ dysfunction syndrome (MODS), which results from a dysfunctional inflammatory response after injury. Previous studies suggest that hypertonic saline may be beneficial by modulating this initial response and decreasing subsequent organ injury. This project takes advantage of a unique opportunity, afforded by an NIH-funded multi-center clinical trial of hypertonic resuscitation (conducted by the Resuscitation Outcomes Consortium), to obtain blood samples from patients enrolled in this trial to analyze inflammatory responses early after hypertonic vs. conventional resuscitation.

The proposed study will be carried out in experiments grouped in three Specific Aims: Aim 1 provides a thorough investigation of the immunomodulatory response following hypertonic resuscitation with regard to neutrophil, monocyte, and T cell responses at serial time points after injury and resuscitation. Aim 2 comprises experiments to investigate the mechanisms by which hypertonicity may alter inflammatory cell signaling. Aim 3 seeks to correlate the laboratory findings with clinical endpoints reflective of immune dysfunction including inflammation, organ failure, nosocomial infection, and sepsis.

The investigators hypothesize that hypertonic resuscitation will be associated with modulation of the excessive inflammatory response seen after injury and thus will result in reduced rates of inflammatory organ injury.

Patients enrolled in clinical trial of Hypertonic Resuscitation based on prehospital evidence of hypovolemic shock or severe brain injury

• Hemorrhagic Shock
• Traumatic Brain Injury

• I
  Hypertonic resuscitation
• 2
  Normal saline resuscitation

Inclusion Criteria:

• Blunt or Penetrating trauma with prehospital systolic blood pressure < 70 or 70-90 mmHg with Heart rate > 108 OR Blunt trauma with prehospital Glasgow coma score <= 8

Exclusion Criteria:

• Age < 15 yrs
• Known prisoners
• Pregnancy
• Ongoing CPR
• Burns < 20%
• Hypothermia < 28 C
• > 2 liters intravenous fluid prior to study fluid administration
• > 4 hour from time of dispatch