Intrathoracic Pressure Regulation for the Treatment of Septic Shock

胸内压力调节治疗感染性休克

• 批准号: 7671152
• 负责人: KEITH G LURIE
• 金额: $ 18.15万
• 依托单位: ADVANCED CIRCULATORY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7671152
• 关键词: Accident and Emergency department; Adverse effects; American; Animals; Applications Grants; Atmospheric Pressure; Blood; Blood Circulation; Blood Pressure; Cardiac; Cardiac Output; Cause of Death; Cell Death; Cerebral perfusion pressure; Chest; Clinical; Clinical Trials; Collaborations; Control Animal; Convulsive therapy; Coronary Care Units; Country; Data; Devices; Diagnosis; Early treatment; Echocardiography; Emergency Situation; Environmental air flow; Failure; Family suidae; Goals; Heart; Heart Arrest; Heart Atrium; Hemorrhagic Shock; Hospital Mortality; Hospitals; Hour; Hypotension; IV Fluid; Income; Inflammatory Response; Injury; Intensive Care Units; Intervention; Intracranial Pressure; Left; Life; Liquid substance; Lung; Measures; Mechanical ventilation; Microcirculation; Modeling; Morbidity - disease rate; Neurologic; Organ; Organ failure; Output; Oxygen; Patients; Perfusion; Peritonitis; Phase; Phase I Clinical Trials; Physiologic pulse; Physiological; Pilot Projects; Protocols documentation; Pulmonary artery structure; Randomized; Randomized Controlled Trials; Regulation; Relative (related person); Renal function; Research; Research Proposals; Resistance; Rest; Resuscitation; Right Ventricular Function; Safety; Sepsis; Septic Shock; Small Business Innovation Research Grant; Stroke Volume; Survival Rate; Survivors; Technology; Therapeutic Intervention; Time; United States; Urine; Vacuum; Vasoconstrictor Agents; Venous; Video Microscopy; Wood material; Work; base; cell injury; clinical practice; design; hemodynamics; improved; innovation; medical schools; mortality; novel; novel therapeutic intervention; pre-clinical; pressure; prevent; prototype; public health relevance; research study; respiratory; restoration; septic

DESCRIPTION (provided by applicant): Despite advances in the treatment of patients with sepsis, sepsis remains the second most common cause of death in non-coronary intensive care units and the tenth leading cause of death overall in high-income countries. It has been estimated that >750,000 cases of severe sepsis occur annually in the United States, with a hospital mortality rate of ~35%. This number continues to grow annually. Nearly half of these septic patients develop severe sepsis and septic shock. In most hospitals more than 60% of severe sepsis patients present to the emergency department. Mortality increases along the sepsis continuum from approximately 25- 30% in severe sepsis and 40-70% in septic shock, and seems to be associated mainly with the amount of multi-organ failure. The goal of this SBIR Phase 1 application is to apply a new potentially life-saving therapy, Intrathoracic Pressure Regulation (IPR) recently developed and shown to increase circulation and survival rates in hemorrhagic shock and cardiac arrest, during the early resuscitation phase of sepsis. Based upon recent animal studies showing that non-invasive IPR can increase vital organ perfusion in states of severe hypotension, the goal of this research is to demonstrate proof of concept in a porcine model of septic shock that when IPR is applied during the initial hemodynamic stabilization treatment phase of sepsis, that key hemodynamic parameters will improve and short-term survival rates will increase. The new device is inserted within a standard respiratory circuit between the patient and a means to ventilate the patient. It functions by decreasing intrathoracic pressure during the expiratory phase to subatmospheric levels after each positive pressure ventilation. The decrease in intrathoracic pressure creates a negative pressure gradient between the thorax relative to the rest of the body thereby a) enhancing venous blood return to the heart b) increasing cardiac output and systemic arterial blood pressure, c) lowering right atrial and pulmonary artery pressures, and d) lowering intracranial pressure and thus further increasing cerebral perfusion pressure. The specific aims of this proposal include: 1) an animal study to demonstrate significant hemodynamic benefit and improved 24 hour survival in a porcine model of peritonitis, 2) an animal study to demonstrate that microcirculation, renal function, and cardiac function can be improved with IPR therapy, and 3) further design work to prototype a variable resistor to allow for adjustments in the intrathoracic vacuum achieved with the IPR and additional design work to prototype a secondary safety mechanism to prevent excessively low intrathoracic pressures by inadvertent user misuse. It is anticipated that a positive Phase 1 Study would provide sufficient preclinical data to support a Phase 2 grant application which would include a clinical trial. This potentially pioneering technology would serve in a complimentary manner with newer goal-directed resuscitation therapies to further reduce the currently excessively high morbidity and mortality for hundreds of thousands of American annually. In real terms, a potential 10% reduction in mortality relates could result in saving 50,000-100,000 lives annually in the United States alone. PUBLIC HEALTH RELEVANCE: Sepsis remains the second most common cause of death in non-coronary intensive care units and the tenth leading cause of death overall in high-income countries. It has been estimated that >750,000 cases of severe sepsis occur annually in the United States, with a hospital mortality rate of ~35%. The goal of this Phase 1 SBIR application is to determine whether the intrathoracic pressure regulator (ITPR), a novel device intended to increase circulation and blood pressure in states of significant hypotension, is a potential therapy for septic shock patients. This potentially pioneering technology would serve in a complimentary manner with newer goal-directed resuscitation therapies to further reduce the currently excessively high morbidity and mortality for hundreds of thousands of American annually. In real terms, a potential 10% reduction in mortality relates could result in saving 50,000-100,000 lives annually in the United States alone.

描述（由申请人提供）：尽管败血症患者的治疗进展，但败血症仍然是非临床重症监护病房中第二大常见的死亡原因，以及高收入国家的第十个主要死亡原因。据估计，在美国，每年发生> 750,000例严重败血症病例，医院死亡率约为35％。这个数字每年继续增长。这些败血症患者中有将近一半出现严重的败血症和败血性休克。在大多数医院中，有60％以上的严重败血症患者出席了急诊科。败血症连续体的死亡率从严重败血症中的大约25-30％和败血性休克中的40-70％增加，似乎主要与多器官衰竭量有关。 SBIR 1阶段应用的目的是应用新的潜在挽救生命的疗法，胸前压力调节（IPR）最近开发的，并显示出在败血症早期复苏阶段提高出血性休克和心脏骤停的循环和存活率。基于最近的动物研究表明，非侵入性IPR可以增加严重低血压状态的重要器官灌注，这项研究的目的是在脓毒症的猪群猪群模型中证明概念证明，当初始血液动力学稳定治疗阶段应用IPR时，关键的血液动力学参数将会提高和短期生存率。新设备被插入患者和通气患者的方法之间的标准呼吸道中。它通过在每次正压通气后降低肠内压力到下大度圈水平的胸腔压力来发挥作用。胸内压力的降低会在胸腔之间相对于身体其余部分产生负压梯度，从而a）增强静脉血液恢复到心脏b）增加心输出量和全身性动脉血压，c）降低右心房和肺动脉压力，d）降低脑压内压，从而降低脑压内压，从而进一步增加塞多内压。 The specific aims of this proposal include: 1) an animal study to demonstrate significant hemodynamic benefit and improved 24 hour survival in a porcine model of peritonitis, 2) an animal study to demonstrate that microcirculation, renal function, and cardiac function can be improved with IPR therapy, and 3) further design work to prototype a variable resistor to allow for adjustments in the intrathoracic vacuum achieved with the IPR and additional design work to原型是一种二级安全机制，可通过无意用户滥用来防止过度低的胸腔压力。可以预计，一项积极的1阶段研究将提供足够的临床前数据来支持2期赠款应用，其中包括临床试验。这项潜在的开创性技术将以免费的方式提供新的目标复苏疗法，以进一步降低目前每年数十万美国人的发病率和死亡率过高。实际上，仅在美国，潜在的降低死亡率降低可能会导致每年挽救50,000-100,000人的生命。公共卫生相关性：败血症仍然是非冠军重症监护病房中第二大最常见的死亡原因，也是高收入国家的第十个主要死亡原因。据估计，在美国，每年发生> 750,000例严重败血症病例，医院死亡率约为35％。该阶段1 SBIR应用的目的是确定胸前压力调节剂（ITPR）是一种旨在增加明显低血压状态的循环和血压的新装置，是败血性休克患者的潜在疗法。这项潜在的开创性技术将以免费的方式提供新的目标复苏疗法，以进一步降低目前每年数十万美国人的发病率和死亡率过高。实际上，仅在美国，潜在的降低死亡率降低可能会导致每年挽救50,000-100,000人的生命。

项目成果

Biphasic intra-thoracic pressure regulation augments cardiac index during porcine peritonitis: a feasibility study.

双相胸内压力调节可增加猪腹膜炎期间的心脏指数：一项可行性研究。

• DOI: 10.3109/03091902.2013.857733
• 发表时间: 2014
• 期刊: Journal of medical engineering & technology
• 作者: Cinel,Ismail;Goldfarb,RoyD;Metzger,Anja;Lurie,Keith;Jasti,Purnachandra;Knob,ChristopherR;Parrillo,JosephE;PhillipDellinger,R
• 通讯作者: PhillipDellinger,R