Novel non-invasive device for treatment of elevated intracranial pressures

描述(由申请人提供)： 据估计，美国每年有160万人头部受伤。每年，每1000名美国人中就有3人受到创伤性脑损伤的影响，导致多达6万人死亡，估计有7万至9万名永久性神经残疾患者。尽管头部损伤患者的治疗取得了进展，但创伤性脑损伤仍是导致儿童、处于生产力最高年龄段的成年人和我们的士兵死亡和残疾的主要原因。这些伤害在生产力损失和医疗费用方面的经济后果是巨大的。虽然最近二十年的研究使人们对导致继发性神经元损伤的生理事件有了更多的了解，但在治疗颅内压升高和脑血流灌注减少的继发性脑损伤方面仍需取得进展。申请人最近开发了一种新的设备，以降低颅内压和增加大脑灌注压。新的非侵入性设备被插入到患者和用于患者通风的装置(例如，机械呼吸机)之间的标准呼吸回路中。它的功能是在呼气期将胸腔内压降低到大气下水平，并提供一种提供正压通风的手段。胸内压的降低，通常为-7至-9毫米汞柱，在胸腔内形成相对于身体其他部分的真空，从而a)增加血液回流到心脏，从而增加心输出量和血压，b)降低颅内压，从而增加脑血流。使用胸内压调节器(ITPR)旨在显著改善患者的预后，这是基于一种增加流向心脏和大脑的血液的独特方式。在第一阶段研究中，研究人员1)证实了ITPR装置在动物身上的安全性和概念性，证明在实质性和潜在致命的颅脑损伤后的第一个小时使用ITPR有助于维持大脑的代谢稳定，比仅使用标准复苏液更好；2)将胸内压真空计整合到ITPR系统中，并通过定制的数字显示界面来跟踪颅内压和胸压等重要生理变量，从而开始研究闭环系统；3)该装置获得了510K的许可。这项第二阶段的研究应用建议：1)证明临床概念，证明应用ITPR将导致神经重症监护病房中头部损伤患者的颅内压下降和脑灌注压增加；2)设计和制作一种增强型、可变真空版本的ITPR，具有独立的真空源和电源，用于手术室和重症监护病房。如果在这些第二阶段研究中显示出显著的临床益处，ITPR有望提供一种全新的工具来增加脑血流，从而降低颅内压升高患者的发病率和死亡率，包括遭受创伤性脑损伤和中风的患者。 公共卫生相关性： 尽管头部损伤患者的治疗取得了进展，但创伤性脑损伤(TBI)仍是儿童和成年人在其生产力最高的年龄段导致死亡和残疾的主要原因。它也是军队发病率和死亡率的主要原因。据估计，美国每年有160万人头部受伤。每年，每1000名美国人中就有3人受到创伤性脑损伤的影响，导致多达6万人死亡，估计有7万至9万名永久性神经残疾患者。尽管头部损伤患者的治疗取得了进展，但创伤性脑损伤仍是导致儿童、处于生产力最高年龄段的成年人和我们的士兵死亡和残疾的主要原因。这些伤害在生产力损失和医疗费用方面的经济后果是巨大的。虽然最近二十年的研究使人们对导致继发性神经元损伤的生理事件有了更多的了解，但在治疗颅内压升高和脑血流灌注减少的继发性脑损伤方面仍需取得进展。申请人最近开发了一种新的设备，以降低颅内压和增加大脑灌注压。新的非侵入性设备被插入到患者和用于患者通风的装置(例如，机械呼吸机)之间的标准呼吸回路中。它的功能是在呼气期将胸腔内压降低到大气下水平，并提供一种提供正压通风的手段。胸内压的降低，通常为-7至-9毫米汞柱，在胸腔内形成相对于身体其他部分的真空，从而a)增加血液回流到心脏，从而增加心输出量和血压，b)降低颅内压，从而增加脑血流。该项目的目标是在颅内压升高的患者群体中展示临床概念的证据。如果在这些第二阶段研究中显示出显著的临床益处，ITPR有望提供一种全新的工具来增加脑血流，从而降低颅内压升高患者的发病率和死亡率，包括遭受创伤性脑损伤和中风的患者。

DESCRIPTION (provided by applicant): An estimated 1.6 million head injury occurs every year in the United States. Traumatic brain injury affects 3 out of every 1000 Americans each year accounting for as many as 60,000 deaths and an estimated 70,000 to 90,000 patients with permanent neurologic disabilities. Despite advances in the treatment of patients with head injuries, traumatic brain injury is the leading cause of death and disability in children, adults in their most productive years, and our soldiers in the military. The economic consequence of these injuries in terms of both lost productivity and the cost of medical care are enormous. While the last two decades of research has resulted in a greater understanding of the physiologic events leading to secondary neuronal injury, advances are needed in the treatment of elevated intracranial pressure and decreased cerebral perfusion secondary brain injury. The applicants recently developed a novel device to decrease intracranial pressure and increase in cerebral perfusion pressures. The new non-invasive device is inserted within a standard respiratory circuit between the patient and a means to ventilate the patient (e.g. mechanical ventilator). It functions by cycling between lowering intrathoracic pressure during the expiratory phase to subatmospheric levels and providing a means to provide positive pressure ventilation. The decrease in intrathoracic pressure, typically to -7 to -9 mmHg, creates a vacuum within the thorax relative to the rest of the body thereby a) enhancing blood return to the heart and consequently increasing cardiac output and blood pressure and b) lowering intracranial pressure thereby increasing cerebral perfusion. Use of the intrathoracic pressure regulator (ITPR) is intended to significantly improve patient outcomes, based upon a unique way to increase in blood flow to the heart and brain. Phase 1 studies, the investigators 1) Established safety and proof of concept of the ITPR device in animals by demonstrating that use of the ITPR in the first hour after a substantial and potentially lethal brain injury helped to maintain metabolic stability of the brain better than standard resuscitation fluid alone; 2) Incorporated an intrathoracic pressure vacuum gauge into the ITPR system and begun work on a closed loop system by prototyping a custom digital display interface that tracks important physiological variables like intracranial pressure and intrathoracic pressure and 3) Received 510k clearance of the device. This phase 2 research application proposes to 1) Demonstrate proof of clinical concept that application of the ITPR will result in a decrease in intracranial pressure and an increase in cerebral perfusion pressure in patients with head injury in a neuro-intensive care unit; and 2) Design and prototype an enhanced, variable vacuum version of the ITPR with self-contained vacuum source and power supply for use in the OR and ICU. If a significant clinical benefit is demonstrated in these Phase 2 investigations, the ITPR promises to provide a fundamentally new tool to increase cerebral perfusion and thus reduce morbidity and mortality in patients with increased intracranial pressures, including patients who suffer from traumatic brain injury and stroke. PUBLIC HEALTH RELEVANCE: Despite advances in the treatment of patients with head injuries, traumatic brain injury (TBI) is the leading cause of death and disability in children and adults in their most productive years. It is also a leading cause of morbidity and mortality in the military. An estimated 1.6 million head injury occurs every year in the United States. Traumatic brain injury affects 3 out of every 1000 Americans each year accounting for as many as 60,000 deaths and an estimated 70,000 to 90,000 patients with permanent neurologic disabilities. Despite advances in the treatment of patients with head injuries, traumatic brain injury is the leading cause of death and disability in children, adults in their most productive years, and our soldiers in the military. The economic consequence of these injuries in terms of both lost productivity and the cost of medical care are enormous. While the last two decades of research has resulted in a greater understanding of the physiologic events leading to secondary neuronal injury, advances are needed in the treatment of elevated intracranial pressure and decreased cerebral perfusion secondary brain injury. The applicants recently developed a novel device to decrease intracranial pressure and increase in cerebral perfusion pressures. The new non-invasive device is inserted within a standard respiratory circuit between the patient and a means to ventilate the patient (e.g. mechanical ventilator). It functions by cycling between lowering intrathoracic pressure during the expiratory phase to subatmospheric levels and providing a means to provide positive pressure ventilation. The decrease in intrathoracic pressure, typically to -7 to -9 mmHg, creates a vacuum within the thorax relative to the rest of the body thereby a) enhancing blood return to the heart and consequently increasing cardiac output and blood pressure and b) lowering intracranial pressure thereby increasing cerebral perfusion. The goal of this project is to demonstrate proof of clinical concept in a patient population with elevated intracranial pressures. If a significant clinical benefit is demonstrated in these Phase 2 investigations, the ITPR promises to provide a fundamentally new tool to increase cerebral perfusion and thus reduce morbidity and mortality in patients with increased intracranial pressures, including patients who suffer from traumatic brain injury and stroke.