Conventional resuscitation of hypovolemic shock following traumatic injury involves the rapid administration of large volumes of lactated ringers (LR) solution. Previous research suggests that initial resuscitation with a hypertonic solution will result in more rapid restoration of blood pressure, improved cerebral perfusion, and modulation of the systemic inflammatory response to ischemia/reperfusion injury. This proposal seeks to evaluate the clinical outcome and inflammatory cell function of patients in shock following blunt traumatic injury who are randomized to receive 7.5% hypertonic saline/6% dextran (HSD) followed by LR versus LR alone. We hypothesize that HSD resuscitation will inhibit the initial excessive systemic activation of the inflammatory response, which will translate into a reduction in the incidence of organ dysfunction induced by this response. Furthermore, we seek to evaluate the impact of HSD resuscitation on recovery following traumatic brain injury, as previous studies suggest that this subgroup has the greatest survival advantage from this intervention.
The specific aims for this proposal include:
Aim 1 : To determine the impact of pre-hospital administration of hypertonic saline/dextran on the development of organ failure following blunt traumatic injury with hypovolemic shock.
Aim 2 : To determine the impact of prehospital administration of hypertonic saline/dextran on the neurologic outcome following brain injury"""""""" for patients in hypovolemic shock.
Aim 3 a: To determine the effect of prehospital administration of hypertonic saline/dextran on the activation of circulating neutrophils and monocytes.
Aim 3 b: To determine the effect of prehospital administration of hypertonic saline/dextran on the activation of T lymphocytes. This proposal builds upon previous research which has demonstrated the safety and practicality of this resuscitation strategy in the prehospital environment. A more detailed understanding of the immuno-inflammatory effects of hypertonicity for all patients and the long-term neurologic outcome for patients with brain injury is critical to determining the role of this resuscitation approach in these critically injured patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL073233-02
Application #
6746971
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Goldberg, Suzanne H
Project Start
2003-04-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$436,201
Indirect Cost
Name
University of Washington
Department
Surgery
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Junger, Wolfgang G; Rhind, Shawn G; Rizoli, Sandro B et al. (2012) Resuscitation of traumatic hemorrhagic shock patients with hypertonic saline-without dextran-inhibits neutrophil and endothelial cell activation. Shock 38:341-50
Bulger, Eileen M (2011) 7.5% saline and 7.5% saline/6% dextran for hypovolemic shock. J Trauma 70:S27-9
Bulger, Eileen M; Jurkovich, Gregory J; Nathens, Avery B et al. (2008) Hypertonic resuscitation of hypovolemic shock after blunt trauma: a randomized controlled trial. Arch Surg 143:139-48;discussion 149
Bulger, Eileen M; Cuschieri, Joseph; Warner, Keir et al. (2007) Hypertonic resuscitation modulates the inflammatory response in patients with traumatic hemorrhagic shock. Ann Surg 245:635-41