Induced hypothermic arrest in traumatic shock

创伤性休克中诱导低温骤停

基本信息

批准号：
6921957
负责人：
HASAN B ALAM
金额：
$ 43.75万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2007-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6921957
关键词：
blood /plasma substitute brain injury hemorrhagic shock induced hypothermia ischemia nonhuman therapy evaluation regeneration swine trauma

项目摘要

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）：导致心血管塌陷的出血性休克对常规的心肺复苏方法的反应不佳。即使可以控制出血的来源并恢复循环，持续5分钟或更长的脑缺血会导致严重的脑损伤。尽管进行了进取的手术干预和开放式心脏复苏，但总体生存仍然约为5％。通常，潜在的伤害是可偿还的，但患者死于不可逆转的冲击。在这样的患者中，维持大脑和心脏生存能力的策略足以控制出血，这可能是挽救生命的。这需要一种全新的方法，重点是快速全身保存，代谢过程中的伤害修复逮捕和延迟复苏。目前，低温是在缺血期间保留细胞活力的最有效方法。但是，尚未确定其在创伤性出血的环境中的作用。我们计划使用临床上相关的大型动物模型来测试激发性休克后诱导的体温过低的治疗应用。长期假设：在总体缺血期间，可以在创伤性致死性出血性休克的情况下诱导低温停滞，以维持器官的生存能力。长期目标：在致命不受控制的出血性休克的情况下，建立最佳诱导，维持和逆转全身体温过低的策略。利用低温停止的时期来修复复杂的伤害。具体目标1：确定总体体温过低的最佳诱导率和逆转。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：确定可以通过完全神经系统恢复来维持低温代谢滞留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中的作用。具体目标3：在诱导低温停滞之前，确定不受控制的出血性休克的持续时间，这与良好的神经系统结局兼容。子目标1：证明低温逮捕期可用于修复复杂的多器官损伤。子目标2：开发和测试方法和技术，可以促进创伤性休克的诱导低温停滞。