Hypertonic Modulation of Inflammation Following Injury
Status:
Terminated
Trial end date:
2009-12-01
Target enrollment:
Participant gender:
Summary
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. This study was an ancillary study to the main randomized clinical trial and
thus prospective observational in nature
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.
Details
Lead Sponsor:
National Institute of General Medical Sciences (NIGMS) University of Washington