Intrathoracic Pressure Regulator for Resuscitation

描述（由申请人提供）： 创伤性损伤仍然是1至44岁美国人的头号死因。创伤相关伤害的经济后果估计超过440亿美元的直接成本和每年超过4000亿美元的生产寿命年。虽然大多数患者在到达医院后存活，但迫切需要用于改善创伤后血流动力学的快速有效方法来降低创伤性损伤的死亡率。该第一阶段申请的重点是一种称为胸内压力调节器（ITPR）的新型非侵入性设备，旨在增强无呼吸水肿患者的循环。ITPR的目的是在液体复苏或更明确的护理可用之前“争取时间”。在吸气阻抗阈值装置（ITD）的开发的基础上，ITPR是一种非侵入性胸内压力装置，其被申请人设计并证明用于增加心脏骤停患者的存活率并增加能够自主呼吸的水肿患者的血压，其快速增加严重水肿患者的循环和血压。ITPR连接到患者的气道，产生小但持续的胸内负压，从而在不提供间歇性正压通气时通过将更多的静脉血抽回心脏来立即增加血压。同时该装置降低颅内压。ITPR的初步动物研究表明，平均动脉压以及冠状动脉和脑灌注压随着ITPR的应用而迅速增加。本I期研究提出a）通过a）确定改善循环所需的最佳真空度，B）对当前原型进行生物工程设计变更并进行评价，以及c）通过在猪出血性休克模型中评估使用和不使用ITPR的神经系统完整存活率和肺部并发症发生率来证明概念验证，从而提高ITPR的安全性和有效性。如果成功，2期研究将探讨ITPR在出血性休克患者中的潜在临床疗效。基于动物研究中观察到的心脏和大脑血流的改善，预计ITPR的使用将显著提高患者复苏率。如果证明了显著的临床益处，ITPR将成为创伤性损伤和其他原因引起的低血容量性低血压患者的标准复苏设备。

DESCRIPTION (provided by applicant): Traumatic injury remains the number one cause of death for Americans between 1 and 44 years of age. The economic consequences of trauma related injuries are estimated at over 44 billion dollars in direct costs and over 400 billion dollars per year in productive life years. While most patients survive after arrival to the hospital, rapid and effective methods for improving hemodynamics after traumatic injury are urgently needed to reduce mortality rates from traumatic injury. This Phase 1 application is focused on a novel non-invasive device called the intrathoracic pressure regulator (ITPR), designed to enhance circulation in non-breathing hypotensive patients. The ITPR is designed to "buy time" before fluid resuscitation or more definitive care is available. Building upon the development of the inspiratory impedance threshold device (ITD), designed and demonstrated by the applicants to increase survival rates in patients in cardiac arrest and to increase blood pressure in hypotensive patients who are able to breathe spontaneously, the ITPR is a non-invasive intrathoracic pressure device that rapidly increases circulation and blood pressure in severely hypotensive patients. The ITPR attaches to the patient's airway, generates a small but continuous negative intrathoracic vacuum and thereby immediately increases blood pressure by drawing more venous blood back into the heart when not providing intermittent positive pressure ventilation. Simultaneously this device lowers intracranial pressure. Preliminary animal studies with the ITPR demonstrate that mean arterial pressures as well as coronary and cerebral perfusion pressures are rapidly increased with application of the ITPR. This Phase 1 investigation proposes to a) improve the safety and efficacy of the ITPR by a) determining the optimal vacuum needed to improve circulation, b) making and evaluating bioengineering design changes in the current prototype and c) demonstrating proof of concept by assessing neurologically intact survival rates and pulmonary complication rates with and without the ITPR in a porcine model of hemorrhagic shock. If successful, Phase 2 studies will address the potential clinical efficacy of the ITPR in patients in hemorrhagic shock. Use of the ITPR is expected to significantly increase patient resuscitation rates, based upon the improvement in blood flow to the heart and brain observed in animal studies. If a significant clinical benefit is demonstrated, the ITPR would become a standard piece of resuscitation equipment for hypotensive patients with traumatic injury and other causes of hypovolemic hypotension.