Novel non-invasive device for treatment of elevated intracranial pressures

用于治疗颅内压升高的新型非侵入性装置

• 批准号: 8136511
• 负责人: KEITH G LURIE
• 金额: $ 31.74万
• 依托单位: ADVANCED CIRCULATORY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-24 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8136511
• 关键词: Accounting; Adult; Affect; American; Animals; Antihypertensive Agents; Area; Blood; Blood Circulation; Blood Pressure; Blood flow; Brain; Brain Injuries; Breathing; Carbon Dioxide; Cardiac; Cardiac Output; Cardiopulmonary; Cardiopulmonary Resuscitation; Cardiovascular system; Cause of Death; Cerebral perfusion pressure; Cerebrovascular Circulation; Cerebrum; Cessation of life; Chest; Chest wall structure; Child; Clinical; Clinical Data; Collaborations; Coma; Craniocerebral Trauma; Custom; Data; Development; Devices; EFRAC; Echocardiography; Economics; Engineering; Enrollment; Environmental air flow; Evaluation; Event; Exhalation; Generations; Goals; Heart; Heart Arrest; Heart Rate; Hemorrhagic Shock; Hospitals; Hour; Human; Hypotension; Hypovolemics; Individual; Injury; Institutes; Intensive Care Units; Intracranial Hypertension; Intracranial Pressure; Investigation; Left; Liquid substance; Lung Compliance; Mechanical Ventilators; Medical; Medical Care Costs; Metabolic; Military Personnel; Morbidity - disease rate; Neurologic; Neuronal Injury; Organ; Outcome; Patient Care; Patients; Performance; Perfusion; Phase; Physiologic pulse; Physiological; Physiology; Power Sources; Productivity; Recording of previous events; Relative (related person); Research; Research Design; Research Personnel; Resistance; Rest; Resuscitation; Safety; Secondary to; Small Business Innovation Research Grant; Soldier; Source; Stroke; Stroke Volume; Survival Rate; System; Technology; Testing; Therapeutic; Traumatic Brain Injury; United States; United States National Aeronautics and Space Administration; Vacuum; Venous; Ventilator; Ventricular End-Diastolic Volumes; Ventricular End-Systolic Volumes; Work; base; clinically relevant; design; digital; disability; electric impedance; hemodynamics; human subject; improved; injured; instrument; interest; middle cerebral artery; monitoring device; mortality; new technology; novel; patient population; phase 1 study; pressure; prognostic indicator; prototype; public health relevance; respiratory; surgical research; therapy development; tool

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.

描述（由申请人提供）： 估计在美国，每年的头部受伤大约160万。每年1000名美国人中，脑外伤会影响3分之3，死亡多达60,000人，估计有70,000至90,000例永久性神经系统疾病。尽管治疗头部受伤患者，但创伤性脑损伤是儿童死亡和残疾的主要原因，成人最有生产力的年份以及我们的军队士兵。这些伤害的经济后果因生产力失去和医疗费用而言都是巨大的。虽然过去的二十年的研究导致对导致继发性神经元损伤的生理事件有了更深入的了解，但在治疗颅内压力升高和降低大脑灌注次级脑损伤方面需要进步。申请人最近开发了一种新型装置，以降低颅内压并增加脑灌注压力。新的非侵入性装置插入了患者和通风患者（例如机械呼吸机）之间的标准呼吸回路中。它通过在呼气阶段降低胸腔压力到亚四圈水平并提供提供正压通气的手段之间的循环作用。胸前压力的降低通常为-7至-9 mmHg，相对于身体其余部分，在胸腔内产生了真空，从而a）增强血液回到心脏，并因此增加心脏输出和血压和血压，b）降低颅内压，从而增加脑力灌注。胸前压力调节器（ITPR）的使用旨在显着改善患者的预后，这是一种独特的方法，可以增加血液流向心脏和大脑的血液。研究人员1）通过证明在实质性且潜在的致命性脑损伤后的第一个小时，在动物中建立了ITPR装置概念的安全性和概念证明，这有助于仅比单独使用标准复苏液保持大脑的代谢稳定性； 2）将胸前压力真空表纳入ITPR系统中，并通过原型制定定制的数字显示界面，开始在封闭环系统上工作，该界面跟踪重要的生理变量，例如颅内压力和胸内压力，3）获得了该设备的510K清除率。该阶段2研究的申请提议1）证明了临床概念证明ITPR的应用将导致颅内压的降低和神经密集型护理部门头部损伤患者的脑灌注压力的升高； 2）设计和原型ITPR的增强，可变的真空版本，具有独立的真空源和电源，可在OR和ICU中使用。如果在这些第2阶段的研究中证明了显着的临床益处，ITPR有望提供一种从根本上提供新工具来增加脑灌注，从而降低颅内压力增加的患者的发病率和死亡率，包括患有脑外伤和中风的患者。 公共卫生相关性： 尽管头部受伤患者的治疗进展，但创伤性脑损伤（TBI）是最有生产力的儿童和成人死亡和残疾的主要原因。这也是军队发病和死亡率的主要原因。估计在美国，每年的头部受伤大约160万。每年1000名美国人中，脑外伤会影响3分之3，死亡多达60,000人，估计有70,000至90,000例永久性神经系统疾病。尽管治疗头部受伤患者，但创伤性脑损伤是儿童死亡和残疾的主要原因，成人最有生产力的年份以及我们的军队士兵。这些伤害的经济后果因生产力失去和医疗费用而言都是巨大的。虽然过去的二十年的研究导致对导致继发性神经元损伤的生理事件有了更深入的了解，但在治疗颅内压力升高和降低大脑灌注次级脑损伤方面需要进步。申请人最近开发了一种新型装置，以降低颅内压并增加脑灌注压力。新的非侵入性装置插入了患者和通风患者（例如机械呼吸机）之间的标准呼吸回路中。它通过在呼气阶段降低胸腔压力到亚四圈水平并提供提供正压通气的手段之间的循环作用。胸前压力的降低通常为-7至-9 mmHg，相对于身体其余部分，在胸腔内产生了真空，从而a）增强血液回到心脏，并因此增加心脏输出和血压和血压，b）降低颅内压，从而增加脑力灌注。该项目的目的是在颅内压力升高的患者人群中证明临床概念的证明。如果在这些第2阶段的研究中证明了显着的临床益处，ITPR有望提供一种从根本上提供新工具来增加脑灌注，从而降低颅内压力增加的患者的发病率和死亡率，包括患有脑外伤和中风的患者。