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Hypertonic Modulation of Inflammation Following Injury

This study has been terminated.
(Enrollment in the clinical trial was stopped for futility)
Information provided by (Responsible Party):
National Institute of General Medical Sciences (NIGMS) Identifier:
First received: September 10, 2008
Last updated: September 23, 2016
Last verified: September 2016

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.

Condition Intervention
Hemorrhagic Shock
Traumatic Brain Injury
Drug: hypertonic saline

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Hypertonic Modulation of Inflammation Following Injury

Resource links provided by NLM:

Further study details as provided by National Institute of General Medical Sciences (NIGMS):

Primary Outcome Measures:
  • neutrophil activation [ Time Frame: ED admission ]
    several parameters of neutrophil activation were assessed

Secondary Outcome Measures:
  • Endothelial cell activation [ Time Frame: ED admission ]
    several parameters of endothelial cell activation were assessed

  • coagulation parameters [ Time Frame: ED admission ]
    several parameters of coagulation were assessed

  • monocyte activation [ Time Frame: ED admission ]
    several parameters of monocyte activation were assessed

Biospecimen Retention:   Samples Without DNA

Enrollment: 119
Study Start Date: November 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Hypertonic saline
Hypertonic resuscitation
Drug: hypertonic 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
Other Name: hypertonic saline with dextran
Control: normal saline
Normal saline resuscitation

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:

Bulger, E. M., Tower, C. M., Bulger, E. M., Garland, T., Cuschieri, J., Rizoli, S., et al. (2011). Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients. Shock (Augusta, Ga.), In press(5), 435-439. doi:10.1097/SHK.0b013e318231ee2e Delano, M. J., Rizoli, S. B., Rhind, S. G., Cuschieri, J., Junger, W., Baker, A. J., et al. (2015). Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypo-Coagulation and Hyper-Fibrinolysis. Shock (Augusta, Ga.), 1. doi:10.1097/SHK.0000000000000368 Junger, W. G., Rhind, S. G., Rizoli, S. B., Cuschieri, J., Baker, A. J., Shek, P. N., et al. (2013). Prehospital hypertonic saline resuscitation attenuates the activation and promotes apoptosis of neutrophils in patients with severe traumatic brain injury. Shock (Augusta, Ga.), 40(5), 366-374. doi:10.1097/SHK.0000000000000038 Junger, W. G., Rhind, S. G., Rizoli, S. B., Cuschieri, J., Shiu, M. Y., Baker, A. J., et al. (2012). Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline-without dextran-inhibits neutrophil and endothelial cell activation. Shock (Augusta, Ga.), 38(4), 341-350. doi:10.1097/SHK.0b013e3182635aca


Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients enrolled in clinical trial of Hypertonic Resuscitation based on prehospital evidence of hypovolemic shock or severe brain injury

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
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Please refer to this study by its identifier: NCT00750997

United States, Washington
University of Washington
Seattle, Washington, United States, 98104
University of Toronto
Toronto, Canada
Sponsors and Collaborators
National Institute of General Medical Sciences (NIGMS)
Principal Investigator: Eileen M Bulger, MD University of Washington
  More Information

Additional Information:
Responsible Party: National Institute of General Medical Sciences (NIGMS) Identifier: NCT00750997     History of Changes
Other Study ID Numbers: R01GM076101-02 ( US NIH Grant/Contract Award Number )
Study First Received: September 10, 2008
Last Updated: September 23, 2016

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Shock, Hemorrhagic
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Plasma Substitutes
Blood Substitutes processed this record on March 28, 2017