Hypertonic Modulation of Inflammation Following Injury

Study Overview
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Brief Summary
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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
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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

Official Title
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Hypertonic Modulation of Inflammation Following Injury

Conditions
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Hemorrhagic Shock, Traumatic Brain Injury

Intervention / Treatment
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* Drug: hypertonic saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertonic saline<br>Hypertonic resuscitation | Drug: hypertonic saline<br>* 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<br>* Other names: hypertonic saline with dextran;|
| Control: normal saline<br>Normal saline resuscitation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neutrophil activation | several parameters of neutrophil activation were assessed | Emergency department admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial cell activation | several parameters of endothelial cell activation were assessed | Emergency department admission | 
| coagulation parameters | several parameters of coagulation were assessed | Emergency department admission | 
| monocyte activation | several parameters of monocyte activation were assessed | Emergency department admission |