Resuscitation--impedance threshold devices in pediatrics

描述(申请人提供)：创伤和低血容量性休克是全球儿童死亡的主要原因。快速、大容量的晶体输注和胸腔内正压通气复苏策略往往会增加出血后的发病率和死亡率。增加胸腔内负压，即使没有液体复苏，也能改善成年猪失血性休克的血流动力学参数和预后。血管生物学、生理学和组织损伤机制随着儿童从婴儿期到青春期的成熟而变化，与成年人明显不同。在儿童严重失血后，恢复血管内容量、防止继发性器官损害、防止可逆性休克进展为不可逆性循环衰竭的最佳方法尚不清楚。我们的中心假设是，通过阻抗阈值装置(ITD)呼吸或在呼吸暂停患者中使用胸腔内压力调节器(ITPR)可以增强胸腔内负压，从而增加前负荷，改善心输出量，增强脑氧合，并延迟或防止婴幼儿可逆性休克到不可逆循环衰竭的进展。这项建议的目的是证明一种新的儿科低血容量性休克复苏策略的概念证明，该策略可以改善预后。该策略包括在婴儿和儿童自主呼吸时使用阻抗阈值装置(ITD)，在需要辅助呼吸机的患者中使用胸腔内压力调节器(ITPR)。两者均可降低胸腔内压，从而增加静脉回流和心输出量，同时降低颅内压。这一阶段的研究计划：1)在失血性休克的儿科模型中确定最佳的ITD“破裂压力”，2)通过在已建立的小儿猪失血性休克模型中评估该装置的能力来证明阻抗阈值阀在儿科猪中的概念：a)改善血流动力学，以及b)提高24小时存活率，以及3)通过在已建立的仔猪失血性休克模型中评估原型来证明胸腔内压调节器(ITPR)在呼吸机依赖的儿科猪中的概念，以证明其能力：a)改善血流动力学，b)提高24小时存活率，和c)使用时没有不良反应，特别是肺不张的发生。最佳的ITD和ITPR复苏策略具有成功抗击低血容量性休克和循环衰竭的巨大潜力，而低血容量性休克和循环衰竭是全球儿童发病率和死亡率的最常见原因。

DESCRIPTION (provided by applicant): Traumatic injury and hypovolemic shock are leading causes of death in children worldwide. Rapid, large volume crystalloid infusion and positive intrathoracic pressure ventilation resuscitation strategies often increase morbidity and mortality following hemorrhage. Augmenting negative intrathoracic pressure, even without fluid resuscitation, improves hemodynamic parameters and outcome in adult porcine hemorrhagic shock. Vascular biology, physiology, and tissue injury mechanisms change as the child matures from infancy through adolescence, and are distinctly different from adults. The optimal method to restore intravascular volume, prevent secondary organ damage, and prevent progression of reversible shock to irreversible circulatory collapse following severe blood loss in children is not known. Our central hypothesis is that breathing through an impedance threshold device (ITD) or, in apneic patients, use of the intrathoracic pressure regulator (ITPR), enhances negative intrathoracic pressure and thus will augment preload, improve cardiac output, enhance cerebral oxygenation, and delay or prevent the progression of reversible shock to irreversible circulatory collapse for infants and children. The goal of this proposal is to demonstrate the proof of concept of a novel resuscitative strategy for hypovolemic shock in pediatrics that improves outcomes. The strategy involves the use of an impedance threshold device (ITD) in spontaneously breathing infants and children and the intrathoracic pressure regulator (ITPR) in patients requiring assisted ventilation. Both lower intrathoracic pressures and thereby enhance venous return and cardiac output while simultaneously lowering intracranial pressures. This phase 1 investigation proposes to: 1) determine the optimal ITD "cracking pressure" in a pediatric model of hemorrhagic shock, 2) demonstrate proof of concept of the impedance threshold valve in pediatric swine by evaluating the device in an established pediatric porcine model of hemorrhagic shock for its ability to: a) improve hemodynamics, and b) increase the 24-hour survival rate, and 3) demonstrate proof of concept of the intrathoracic pressure regulator (ITPR) in ventilator dependent pediatric swine by evaluating the prototype in an established piglet model of hemorrhagic shock for its ability to: a) improve hemodynamics, b) increase the 24-hour survival rate, and c) be used without adverse events, specifically the occurrence of atelectasis. An optimal ITD and ITPR resuscitation strategy has a great potential to successfully combat hypovolemic shock and circulatory collapse, the most common cause of morbidity and mortality in children worldwide.