Induced hypothermic arrest in traumatic shock

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DESCRIPTION (provided by applicant): Hemorrhagic shock that leads to cardiovascular collapse does not respond well to conventional methods of cardiopulmonary resuscitation. Even when the source of bleeding can be controlled and circulation restored, cerebral ischemia lasting 5 minutes or longer results in severe brain damage. Overall survival remains about 5% despite aggressive surgical interventions and open chest cardiac resuscitation. Often the underlying injury is reparable but the patient dies of irreversible shock. In such patients, strategies to maintain cerebral and cardiac viability long enough to gain control of hemorrhage could be life saving. This requires an entirely new approach, with emphasis on rapid total body preservation, repair of injuries during metabolic arrest and delayed resuscitation. Currently, hypothermia is the most effective modality for preservation of cellular viability during periods of ischemia. However, its role in the setting of traumatic hemorrhage has not been established. We plan to use clinically relevant large animal models to test the therapeutic application of induced hypothermia following exsanguinating shock. LONG TERM HYPOTHESIS: Hypothermic arrest can be induced in the setting of traumatic lethal hemorrhagic shock to maintain organ viability during periods of total body ischemia. LONG TERM GOALS: Establish the optimal strategy for induction, maintenance and reversal of total body hypothermia in the setting of lethal uncontrolled hemorrhagic shock. Utilize the period of hypothermic arrest for repair of complex injuries. SPECIFIC AIM 1: Determine the optimal rate of induction and reversal of total body hypothermia. Sub aim: Develop and utilize large animal cognitive function models to test neurologic outcome. SPECIFIC AIM 2: Establish the maximum depth and duration for which hypothermic metabolic arrest can be maintained with complete neurologic recovery. Sub aim: Study the role of optimal a cellular organ preservation fluids in extending the duration of hypothermic metabolic arrest. SPECIFIC AIM 3: Determine the duration of uncontrolled hemorrhagic shock, prior to induction of hypothermic arrest, that is compatible with good neurologic outcome. Sub aim 1: Demonstrate that the hypothermic arrest period can be used to repair complex multiple organ injuries. Sub aim 2: Develop and test methods and techniques that can facilitate the induction of hypothermic arrest in the setting of traumatic shock.