Hypertonic Modulation of Inflammation Following Injury

Terminated

• Conditions: Hemorrhagic Shock; Traumatic Brain Injury
• Interventions: Drug: hypertonic saline

• Registration Number: NCT00750997
• Lead Sponsor: University of Washington

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

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2008-09-10
• Study First Submitted QC: 2008-09-10
• Study First Posted: 2008-09-11
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-27
• Last Update Posted: 2017-05-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 119

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hypertonic saline	hypertonic saline	Hypertonic resuscitation

Primary Outcome Measures

Name	Time	Method
neutrophil activation	Emergency department admission	several parameters of neutrophil activation were assessed

Secondary Outcome Measures

Name	Time	Method
Endothelial cell activation	Emergency department admission	several parameters of endothelial cell activation were assessed
monocyte activation	Emergency department admission	several parameters of monocyte activation were assessed
coagulation parameters	Emergency department admission	several parameters of coagulation were assessed

Trial Locations

Locations (2)

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Toronto; 🇨🇦 Toronto, Canada