Induced hypothermic arrest in traumatic shock

描述（由申请人提供）： 导致心血管衰竭的失血性休克对传统的心肺复苏方法反应不佳。 即使出血源可以得到控制，循环恢复，持续5分钟或更长时间的脑缺血也会导致严重的脑损伤。 尽管进行了积极的外科干预和开胸心脏复苏，总生存率仍保持在5%左右。 通常，潜在的损伤是可以修复的，但患者死于不可逆的休克。在这些患者中，维持大脑和心脏活力足够长时间以控制出血的策略可能是挽救生命的。 这需要一种全新的方法，重点是快速全身保护，修复代谢过程中的损伤， 延迟复苏和延迟复苏。 目前，低温是在缺血期间保存细胞活力的最有效方式。 然而，其在创伤性出血中的作用尚未确定。 我们计划使用临床相关的大型动物模型来测试失血性休克后诱导低温的治疗应用。 长期假设：在创伤致死性失血性休克的情况下，可以诱导低温停搏，以在全身缺血期间维持器官活力。 长期目标：建立诱导、维持和逆转致死性非控制性失血性休克全身低温的最佳策略。 利用低温停搏期修复复杂损伤。 具体目的1：确定诱导和逆转全身低温的最佳速率。 子目标：开发和利用大型动物认知功能模型来测试神经学结果。 具体目标2：确定低温代谢停止的最大深度和持续时间，以保持神经功能完全恢复。 目的：研究最佳细胞器官保存液在延长低温代谢停止时间中的作用。 具体目标3：在诱导低温停搏之前，确定不受控制的失血性休克的持续时间，该持续时间与良好的神经功能结局相一致。 子目标1：证明低温停搏期可用于修复复杂的多器官损伤。 子目标2：开发和测试有助于在创伤性休克情况下诱导低温停搏的方法和技术。

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.