Clinical trial NCT00750997: Hypertonic Modulation of Inflammation Following Injury
Official title: Hypertonic Modulation of Inflammation Following Injury
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Hemorrhagic Shock
Traumatic Brain Injury
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2008-09-11
Enrollment: 119
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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

Eligibility criteria: 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

Primary outcomes:
measure: neutrophil activation
timeFrame: Emergency department admission
Secondary outcomes:
measure: Endothelial cell activation
timeFrame: Emergency department admission
measure: coagulation parameters
timeFrame: Emergency department admission
measure: monocyte activation
timeFrame: Emergency department admission
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Toronto
country: Canada
facility: University of Toronto
Study officials:
affiliation: University of Washington
name: Eileen M Bulger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.