Induced hypothermic arrest in traumatic shock

创伤性休克中诱导低温骤停

• 批准号: 6786769
• 负责人: HASAN B ALAM
• 金额: $ 37.05万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786769
• 关键词: blood /plasma substitute; brain injury; hemorrhagic shock; induced hypothermia; ischemia; nonhuman therapy evaluation; regeneration; swine; trauma

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.

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。 即使可以控制出血源并恢复循环，持续5分钟或更长时间的脑缺血也会导致严重的脑损伤。 尽管采取了积极的手术干预和开胸心脏复苏，总体生存率仍约为 5%。 通常，潜在的伤害是可以修复的，但患者会因不可逆转的休克而死亡。对于此类患者，维持大脑和心脏活力足够长的时间以控制出血的策略可能会挽救生命。 这需要一种全新的方法，重点是快速全身保存、代谢过程中损伤的修复 逮捕和延迟复苏。 目前，低温是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休克后诱导低温的治疗应用。 长期假设：在创伤性致命失血性休克的情况下可以诱导低温骤停，以在全身缺血期间维持器官的活力。 长期目标：建立在致命的失血性休克情况下诱导、维持和逆转全身低温的最佳策略。 利用低温停止期修复复杂损伤。 具体目标 1：确定全身低温的诱导和逆转的最佳速率。 子目标：开发和利用大型动物认知功能模型来测试神经系统结果。 具体目标 2：确定在神经系统完全恢复的情况下可以维持低温代谢停止的最大深度和持续时间。 子目标：研究最佳细胞器官保存液在延长低温代谢停滞持续时间方面的作用。 具体目标 3：确定在诱导低温骤停之前不受控制的失血性休克的持续时间，这与良好的神经系统结果相一致。 子目标 1：证明低温骤停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骤停的方法和技术。