Resuscitation using novel impedance threshold devices in pediatrics

描述（由申请人提供）：创伤性损伤和低血容量性休克是世界范围内儿童死亡的主要原因。快速，大容量晶体输注和胸腔正压通气复苏策略经常增加出血后的发病率和死亡率。增加胸内负压，即使不进行液体复苏，也能改善成年猪失血性休克的血流动力学参数和预后。血管生物学、生理学和组织损伤机制随着儿童从婴儿期到青春期的成熟而变化，并且与成人有明显不同。恢复血管内容量，防止继发性器官损伤，防止儿童严重失血后可逆休克发展为不可逆循环衰竭的最佳方法尚不清楚。我们的中心假设是，使用胸内压力调节（IPR）可以增强胸内负压，从而增加预负荷，改善心输出量，增强脑氧合，延缓或防止婴儿和儿童从可逆性休克发展为不可逆循环衰竭。IPR治疗通过调节无呼吸患者的胸内压力起作用。每次正压通气后，将胸内压降至亚大气压水平（-5至-12 cmH2O）。降低胸内压使静脉血回流心脏，降低颅内压，从而增加全身和脑灌注。由于心输出量增加，颅内对向前血流的阻力降低，脑灌注增加。这种新疗法使用一个外部真空源来降低胸内压力，并根据需要使用一个开关来允许间歇性正压通气。仔细滴定胸内负压

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. PUBLIC HEALTH RELEVANCE: Trauma-induced hemorrhagic shock is the leading cause of hypotension in both children and adults. Multi-system trauma accounts for 50% of deaths occurring in children, most often from blunt trauma with severe hypovolemia progressing to circulatory collapse (CDC Vital Statistics 2003). For every pediatric patient that dies as a result of trauma, there are four survivors who are permanently disabled (approximately 100,000/year in the USA). Regardless of the etiology, intractable cardiovascular collapse continues to be a significant clinical challenge, especially in critically ill patients despite traditional fluid resuscitation and vasopressor agents. The main objective of this Phase 2 proposal is to provide proof of concept evidence in a carefully designed clinical study that application of intrathoracic pressure regulation (IPR) therapy will result in an increase in cardiac index and cerebral oxygenation in pediatric patients: a) with sepsis or b) who have undergone cardiac surgery for congenital heart disease (CHD) (single ventricle or tetralogy of Fallot). New approaches to treatment for this common medical emergency have the potential to reduce the high morbidity and mortality rates associated with severe hypotension. As such, this new device has the potential to be an important new advance in treating life-threatening hypotension and thereby reduce pediatric morbidity and mortality rates.