Hypertonic Modulation of Inflammation following Injury

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DESCRIPTION (provided by applicant): This is a proposal to determine the effect of prehospital hypertonic resuscitation vs. conventional resuscitation with crystalloid on the inflammatory response early after injury. The leading cause of late mortality following injury is multiple organ dysfunction syndrome, which results from dysfunctional inflammatory response of the patient early after injury. Previous studies, suggest that hypertonic saline may be beneficial in modulating this initial response and thus decrease the subsequent organ injury. These effects, which have been well described in the laboratory, have yet to be proven in humans, particularly in the setting of severe injury. This proposal takes advantage of a unique opportunity to obtain blood samples from patients enrolled in a NIH supported multi-center trial of hypertonic resuscitation and analyze their inflammatory responses early after injury. The proposed trial is to be conducted by the Resuscitation Outcomes Consortium (ROC), which consists often clinical centers in the US and Canada. This study is a three arm, blinded, randomized trial comparing 7.5% saline, 7.5% saline/6% dextran-70 and normal saline (0.9%) as the initial resuscitation fluid administered to patients in hypovelemic shock or with signs of sever traumatic brain injury. Three of the ROC clinical sites will collaborate to study then inflammation response of patients enrolled at theses sites. The specific aims include: Aim 1: To profile and characterize the phenotype of the innate and cellular immune systems in response to hypertonic resuscitation following injury. Aim 2: To define, in humans, the cellular mechanisms responsible for hypertonic modulation of the inflammatory response. Aim 3: To determine whether immunologic changes observed following hypertonic resuscitation associated with differences in clinical outcome as manifested by the development of organ dysfunction, and nosocomial infection. The results of these studies will provide valuable information to determine the ultimate therapeutic use of the resuscitation strategy.