Hemorrhagic Shock, Traumatic Brain Injury
Conditions
Brief 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.
Detailed description
This was an ancillary study to the larger clinical trials of prehospital hypertonic resuscitation conducted by the resuscitation outcomes consortium. This study investigated markers of immune function and coagulation in a subset of patients enrolled in the larger trials at two of the clinical sites. Four publications detail the results please see references
Interventions
DRUGhypertonic saline
patients in parent trial were randomized to 250cc 7.5% saline, 7.5%saline with 6%dextran or normal saline as control as the initial resuscitation fluid after injury with signs of either hemorrhagic shock or severe traumatic brain injury
Sponsors
University of Washington
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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 Cardiopulmonary resuscitation (CPR) * Burns \< 20% * Hypothermia \< 28 C * \> 2 liters intravenous fluid prior to study fluid administration * \> 4 hour from time of dispatch
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| neutrophil activation | Emergency department admission | several parameters of neutrophil activation were assessed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial cell activation | Emergency department admission | several parameters of endothelial cell activation were assessed |
| coagulation parameters | Emergency department admission | several parameters of coagulation were assessed |
| monocyte activation | Emergency department admission | several parameters of monocyte activation were assessed |
Countries
Canada, United States
Outcome results
None listed