Rapid Induction of Therapeutic Hypothermia

描述（由申请人提供）：该项目将介绍一种全新的方法，用于诱导轻度低温和脑冷却。治疗性低温（TH）以前已被证明可以改善患者的生存和神经系统的结果，但它只被一小部分医疗保健系统采用。缺乏采用，部分原因是由于不切实际，无效或干扰EMS复苏工作的实施方法不佳。该项目将测试和演示一种新型的经鼻蒸发冷却装置，解决这些问题，这将有助于更广泛的水平， 采用和使用治疗。目前的诱导技术依赖于某种形式的主动冷却，无论是通过冰袋、冷盐水还是蒸发流体。我们的方法是新颖的，因为我们正在利用一个生理过程，触发身体冷却自己。没有主动冷却系统或蒸发化学品。我们的冷却方法仅使用干燥的环境空气。上呼吸道在调节吸入的空气（在到达肺部之前）方面非常有效，即，它能很快将干燥空气加湿到饱和状态。这一过程需要能量将体内的水转化为蒸汽，然后与进入的干燥空气混合。我们的冷却方法使用这种生理反应来实现所需的低温。我们迫使干燥的空气通过鼻道，然后提取潮湿的空气， 能量和热量排出体外。该项目将分几个连续阶段完成。在第一阶段，我们将在猪的初步研究的基础上，优化冷却过程变量，研究一系列空气流量和温度。我们还将开发一个简单的原型设备来提供治疗，并确认该方法的安全性。在第二阶段，我们将开发一种临床级设备，并进行额外的猪研究，以确认诱导低温是安全、有效的，并与复苏和短期神经功能改善的结果相关。我们将以一项小型人体研究结束第二阶段，以评估该过程在人类中的安全性，耐受性和有效性。这项工作将验证一种诱导低温的新方法，该方法可以在院外心脏骤停以及其他大脑和心脏缺血性损伤的治疗过程中轻松部署。我们计划继续我们的开发计划，进入更大的临床试验（II期后），以评估在ROSC后早期引入这种疗法的临床益处。最终，我们计划利用这一资助计划来创造一种新的产品和治疗模式，这将具有重大的临床和经济价值。

DESCRIPTION (provided by applicant): This project will introduce a completely new approach for inducing mild hypothermia and cerebral cooling. Therapeutic Hypothermia (TH) has previously been shown to improve patient survival and neurological outcomes, but it has only been adopted by a small fraction of medical healthcare systems. The lack of adoption has, in part, been due to poor implementation methods that are either impractical, ineffective, or they interfere with EMS resuscitation efforts. This project will test and demonstrate a novel trans-nasal evaporative cooling device that solves these issues, which will facilitate a broader level of adoption and use of the therapy. Current induction techniques rely on some form of active cooling, whether by ice packs, cold saline or evaporative fluids. Our approach is novel in that we are harnessing a physiologic process that triggers the body to cool itself. There are no active cooling systems or evaporative chemicals. Our cooling method uses only dry, ambient air. The upper respiratory tract is very efficient at conditioning inspired air (prior to arrival at the luns), i.e., it can humidify dry air to full saturation very quickly. This humidifying process requires energy to convert water in the body to a vapor that is then mixed with the incoming dry air. Our cooling approach uses this physiological response to achieve the desired hypothermia. We force dry air through the nasal track and then extract the moisturized air, which effectively pulls energy and heat out of the body. This project will be completed in several sequential stages. In Phase I, we will build on our preliminary studies with pigs to optimize the cooling process variables, looking at a range of air flows and temperature. We will also develop a simple prototype device to deliver the therapy and to confirm the safety of the method. In Phase II, we will develop a clinical-grade device and perform additional pig studies to confirm that the induced hypothermia is safe, effective and is associated with improved outcome of resuscitation and short term neurologic function. We will end Phase II with a small human study to evaluate the safety, tolerability and efficacy of the process in humans. This work will validate a new method for inducing hypothermia that can be easily deployed during treatment of out-of-hospital cardiac arrest, as well as other ischemic injuries to the brain and the heart. We plan to continue our development program into larger clinical trials (post Phase II) to assess clinical benefits associated with introducing this therapy early after ROSC. Ultimately, we plan to leverage this grant program into the creation of a new product and therapy model that will have significant clinical and economic value.