Resuscitation--impedance threshold devices in pediatrics

描述（由申请人提供）：创伤性损伤和低血容量性休克是全球儿童死亡的主要原因。快速、大量晶体液输注和胸内正压通气复苏策略常增加出血后的发病率和死亡率。在成年猪失血性休克中，即使没有液体复苏，增加胸内负压也能改善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，并且与成人明显不同。目前尚不清楚在儿童严重失血后恢复血管内容量、防止继发性器官损伤和防止可逆性休克进展为不可逆性循环衰竭的最佳方法。我们的中心假设是，通过阻抗阈值装置（ITD）呼吸，或者在窒息患者中使用胸内压力调节器（ITPR），可以增强胸内负压，从而增加前负荷，改善心输出量，增强脑氧合作用，并延迟或防止婴儿和儿童从可逆性休克进展为不可逆性循环衰竭。本提案的目的是证明一种改善儿科低血容量性休克结局的新型复苏策略的概念证明。该策略包括在自主呼吸的婴儿和儿童中使用阻抗阈值装置（ITD），在需要辅助通气的患者中使用胸内压力调节器（ITPR）。两者均降低胸内压，从而增强静脉回流和心输出量，同时降低颅内压。本1期研究旨在：1）确定小儿出血性休克模型中的最佳ITD“开启压力”，2）通过在已建立的小儿出血性休克猪模型中评价器械的以下能力，证明小儿阻抗阈值阀的概念验证：a）改善血液动力学，和B）增加24小时存活率，和3）证明胸内压力调节器（ITPR）的概念验证通过在已建立的出血性休克仔猪模型中评价原型的以下能力：a）改善血液动力学，B）增加24小时存活率，和c）在没有不良事件的情况下使用，特别是肺不张的发生。最佳ITD和ITPR复苏策略具有成功对抗低血容量性休克和循环衰竭的巨大潜力，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.