Resuscitation using novel impedance threshold devices in pediatrics

在儿科中使用新型阻抗阈值设备进行复苏

基本信息

批准号：
8538490
负责人：
KEITH G LURIE
金额：
$ 29.96万
依托单位：
ADVANCED CIRCULATORY SYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8538490
关键词：
Accounting Adolescence Adult Affect Animal Testing Animals Back Biology Blood Blood Vessels Blood flow Blunt Trauma Cardiac Cardiac Output Cardiac Surgery procedures Cardiology Cardiovascular system Cause of Death Centers for Disease Control and Prevention (U.S.)Cerebral Hypoxia Cerebrum Cessation of life Child Childhood Clinical Clinical Data Clinical Research Clinical Trials Collaborations Common Ventricle Critical Care Critical Illness Development Devices Disabled Persons Emergency Situation Engineering Enrollment Environmental air flow Etiology Family suidae Grant Heart Hemorrhage Hemorrhagic Shock High Cardiac Output Hour Housing Hypotension Hypovolemia Hypovolemic Shock Infant Infusion procedures Injury Innovative Therapy Intermittent Positive-Pressure Ventilation Intracranial Hypertension Intracranial Pressure Life Limb structure Liquid substance Low Cardiac Output Syndrome Marketing Measures Medical Methods Modeling Morbidity - disease rate Neurologic Organ Outcome Oxygen Patients Pediatrics Perfusion Phase Physiological Physiology Population Regulation Research Research Personnel Resistance Resuscitation Secondary to Sepsis Septic Shock Shock Source Survivors System Technology Testing Tetralogy of Fallot Therapeutic Tissues Trauma Tube Vacuum Vasoconstrictor Agents Venous Vital Statistics Work brain tissue combat common treatment congenital heart disorder crystalloid design electric impedance endotracheal hemodynamics improved indexing infancy miniaturize mortality novel novel strategies palliation phase 1 study pre-clinical pressure prevent pulmonary function repaired standard of care

项目摘要

DESCRIPTION (provided by applicant): Traumatic injury and hypovolemic shock are leading causes of death in children worldwide. Rapid, large volume crystalloid infusion and positive intrathoracic pressure ventilation resuscitation strategies often increase morbidity and mortality following hemorrhage. Augmenting negative intrathoracic pressure, even without fluid resuscitation, improves hemodynamic parameters and outcome in adult porcine hemorrhagic shock. Vascular biology, physiology, and tissue injury mechanisms change as the child matures from infancy through adolescence, and are distinctly different from adults. The optimal method to restore intravascular volume, prevent secondary organ damage, and prevent progression of reversible shock to irreversible circulatory collapse following severe blood loss in children is no known. Our central hypothesis is that use of intrathoracic pressure regulation (IPR), enhances negative intrathoracic pressure and thus will augment preload, improve cardiac output, enhance cerebral oxygenation, and delay or prevent the progression of reversible shock to irreversible circulatory collapse for infants and children. IPR therapy works by regulating intrathoracic pressures in non-breathing patients. It lowers intrathoracic pressures to subatmospheric levels (-5 to -12 cmH2O) after each positive pressure ventilation. Lowering intrathoracic pressure draws venous blood back to the heart and lowers intracranial pressure, thereby increasing systemic and cerebral perfusion. Cerebral perfusion is increased by decreased intracranial resistance to forward blood flow secondary to higher cardiac output. This novel therapy uses an external vacuum source to lower intrathoracic pressure and a switch to allow for intermittent positive pressure ventilation, as needed. The negative intrathoracic pressure is carefully titrated to optimize benefit with no evidence of harm to date. Building upon the successful Phase 1 studies that demonstrated improved 24 hour neurological survival when utilizing IPR technology in a pediatric porcine hemorrhage model, we propose to evaluate this innovative therapy in a carefully controlled clinical study in the pediatric population and measure key physiological variables including brain tissue oxygen levels. Specifically, the investigators propose to: 1) complete the development of and 510k clear an enhanced, miniaturized pediatric specific version of IPR therapy with variable vacuum levels that is housed in the expiratory limb of a standard ventilation circuit to be utilized in a clinical study, and 2) demonstrate proof of concep that application of intrathoracic pressure regulation (IPR) therapy will result in an increase in cardiac index in pediatric patients: a) with sepsis or b) who have undergone cardiac surgery for congenital heart disease (CHD) (single ventricle or tetralogy of Fallot). IPR resuscitation strategy has the potential to successfully combat hypovolemic shock and circulatory collapse, the most common cause of morbidity and mortality in children worldwide.

描述（由申请人提供）：全球儿童的创伤性损伤和低血症性休克是导致死亡的主要原因。快速，大容量的晶体输注和呈阳性的胸前压力通气复苏策略通常会增加出血后的发病率和死亡率。即使没有液体复苏，也会增加负面的胸腔内压力，可改善成人猪出血性休克的血液动力学参数和结果。随着儿童从婴儿期到青春期的成熟，血管生物学，生理和组织损伤机制发生了变化，并且与成年人明显不同。尚不清楚儿童严重失血后，恢复血管内体积，防止次要器官损害的最佳方法，防止可逆性冲击向不可逆的循环崩溃。我们的中心假设是使用胸前压力调节（IPR），增强负面的胸内压力，从而增加预加载，改善心脏输出，增强大脑氧合，延迟或防止可逆性冲击向婴儿和儿童的不可逆循环循环循环。 IPR疗法通过调节非呼吸患者的静脉压力来进行作业。每次正压通气后，它降低了胸腔内压力到亚四圈水平（-5至-12 CMH2O）。降低胸腔压力可将静脉血恢复到心脏，并降低颅内压，从而增加全身和脑灌注。通过颅内耐药性降低对较高心输出量的前进血流，增加了脑灌注。这种新颖的疗法使用外部真空源来降低胸内压力和开关，以便根据需要进行间歇性正压通风。负胸腔压力仔细滴定优化福利，没有迄今为止危害的证据。基于成功的1阶段研究，该研究表明，在小儿猪出血模型中利用IPR技术时，有改善的24小时神经系统生存率，我们建议在小儿种群中精心控制的临床研究中评估这种创新疗法并测量关键的生理变量，包括脑组织氧气。具体而言，调查人员建议：1）完成和510k的开发和510k的开发清除了一个增强的，微型的小儿特定版本的IPR疗法，具有可变的真空水平，该水平容纳在临床研究的标准通风电路的呼应级别中，并且在临床研究中使用的证据，2）在施加构成的情况下，将置于静脉内疗法（IPR）的应用（ipr），IPR（IPR）的应用程序（IPR）构成IMPR构成的刺激范围（IPR）IMPR（IPR）IPR构成IMPR构成的IMPR构成。患者：a）患有败血症或b）患有先天性心脏病（CHD）的心脏手术（法洛的单脑室或四边形）。知识产权复苏策略有可能成功地打击低血容量的休克和循环崩溃，这是全球儿童发病和死亡率的最常见原因。