Hypertonic Modulation of Inflammation Following Injury

NCT00750997 | Terminated DMC

• 1 other identifier: 28233
• Study Type: observational
• Target: 119
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hemorrhagic Shock; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• neutrophil activation

  several parameters of neutrophil activation were assessed

  Emergency department admission

Secondary Outcomes (3)

• Endothelial cell activation

  Emergency department admission

• coagulation parameters

  Emergency department admission

• monocyte activation

  Emergency department admission

Study Arms (2)

Hypertonic saline

Hypertonic resuscitation

Drug: hypertonic saline

Control: normal saline

Normal saline resuscitation

Interventions

hypertonic saline DRUG

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

Also known as: hypertonic saline with dextran

Hypertonic saline

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead

Study Sites (2)

University of Washington

Seattle, Washington, 98104, United States

Location

University of Toronto

Toronto, Canada

Location

Related Publications (4)

• Delano MJ, Rizoli SB, Rhind SG, Cuschieri J, Junger W, Baker AJ, Dubick MA, Hoyt DB, Bulger EM. Prehospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsens Hypocoagulation and Hyperfibrinolysis. Shock. 2015 Jul;44(1):25-31. doi: 10.1097/SHK.0000000000000368.

  PMID: 25784523 RESULT

• Junger WG, Rhind SG, Rizoli SB, Cuschieri J, Baker AJ, Shek PN, Hoyt DB, Bulger EM. Prehospital hypertonic saline resuscitation attenuates the activation and promotes apoptosis of neutrophils in patients with severe traumatic brain injury. Shock. 2013 Nov;40(5):366-74. doi: 10.1097/SHK.0000000000000038.

  PMID: 24088993 RESULT

• Junger WG, Rhind SG, Rizoli SB, Cuschieri J, Shiu MY, Baker AJ, Li L, Shek PN, Hoyt DB, Bulger EM. Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline-without dextran-inhibits neutrophil and endothelial cell activation. Shock. 2012 Oct;38(4):341-50. doi: 10.1097/SHK.0b013e3182635aca.

  PMID: 22777113 RESULT

• Bulger EM, Tower CM, Warner KJ, Garland T, Cuschieri J, Rizoli S, Rhind S, Junger WG. Increased neutrophil adenosine a3 receptor expression is associated with hemorrhagic shock and injury severity in trauma patients. Shock. 2011 Nov;36(5):435-9. doi: 10.1097/SHK.0b013e318231ee2e.

  PMID: 21841534 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma

MeSH Terms

Conditions

Shock, Hemorrhagic; Brain Injuries, Traumatic

Interventions

Saline Solution, Hypertonic; Dextrans

Condition Hierarchy (Ancestors)

Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates

Study Officials

• Eileen M Bulger, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Surgery

Study Record Dates

• First Submitted: September 10, 2008
• First Posted: September 11, 2008
• Study Start: November 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 1, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)