Use of transnasal air flow to cool and protect the brain after pediatric cardiac arrest

小儿心脏骤停后使用经鼻气流冷却和保护大脑

基本信息

批准号：
9281075
负责人：
RAYMOND Charles KOEHLER
金额：
$ 20.25万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9281075
关键词：
Accident and Emergency department Adaptive Behaviors Adolescent Adult Adverse effects Age Air Animal Model Animals Anterior nares Area Arrhythmia Birth Blood Blood Circulation Blood capillaries Blood flow Body Surface Brain Brain Injuries Brain region Cannulas Cardiopulmonary Resuscitation Cephalic Child Childhood Data Development Encephalopathies External Defibrillator Family suidae Goals Health Personnel Heart Heart Arrest Helmet Histologic Histopathology Hospitals Hour Human Humidifier Hypoxia Incidence Infant Maintenance Measures Medical emergency Modeling Nasal Epithelium Nasal turbinate bone structure Neonatal Nerve Degeneration Nervous System Trauma Neurologic Deficit Neurological outcome Neurons Newborn Animals Newborn Infant Normal Range Nose Oral cavity Outcome Oxidative Stress Paramedical Personnel Pattern Pediatric Hospitals Pre-Clinical Model Prevention Protocols documentation Pulmonary Circulation Rattus Reaction Time Reporting Resources Rest Resuscitation Retrospective Studies Safety Severities Structure of mucous membrane of nose Surface Survivors Taiwan Techniques Temperature Testing Therapeutic Time Toddler Treatment Efficacy Work age group capillary clinical practice clinically relevant cost countercurrent chromatography density experience experimental study functional outcomes hospital discharge rate improved induced hypothermia infant animal innovation juvenile animal mortality natural hypothermia neonatal hypoxic-ischemic brain injury neurological recovery neuronal survival neuroprotection new technology portability programs psychologic public education risk minimization

项目摘要

Despite recent improvements in hospital discharge rates from in-hospital pediatric cardiac arrest, discharge rates and neurologic outcome from out-of-hospital pediatric cardiac arrest remains poor. For adult cardiac arrest victims and newborns with hypoxic-ischemic encephalopathy, hypothermia is the only available treatment, although it does not provide complete neuroprotection in all adults or newborns. For out-of-hospital pediatric cardiac arrest, a recent trial failed to demonstrate improved functional outcome, in part because of the 5.9-hour delay in inducing hypothermia. To minimize this delay, we developed a simple yet innovative technique of transnasal cooling. Dry air at ambient temperature is passed through standard nasal cannula and out of the mouth to produce evaporative cooling of the nasal passages and a countercurrent heat exchange with cephalic arterial blood. An ongoing safety trial in adults indicates the feasibility of reducing core temperature without adverse effects on the nasal passages. Pilot data in large animals relevant to human toddlers and juveniles indicate rapid, uniform and preferential brain cooling compared to the body core. Preliminary work in a newborn animal model of asphyxic cardiac arrest indicates nearly complete histological neuronal protection with early initiation of transnasal cooling. However, the rate of brain cooling was slower in newborn and infant animals than in toddler and juvenile animals, possibly because of a smaller nasal turbinate surface area and underdeveloped nasal capillary density and blood flow. To better define maturational effects, we will study transnasal cooling efficacy after asphyxic cardiac arrest and resuscitation in animals at two ages relevant to infants and toddlers. These age groups have the highest incidence of asphyxic arrest. In Aim 1, we will measure the time course of cooling in different brain regions and body core after resuscitation to assess the effective range of airflow rates that can cool the brain without potential adverse effects on the pulmonary circulation. We will determine whether the brain is cooled uniformly, in contrast to the delayed subcortical cooling attained with cooling helmets. We will also determine whether the brain is cooled more rapidly than the body core. Prevention of overcooling the heart should minimize the risk of arrhythmias. In Aim 2, we will initiate transnasal cooling immediately or two hours after resuscitation and quantify neuronal histopathology in highly vulnerable brain regions to assure efficacy of neuroprotection over a range of clinically relevant delays. We will determine whether the rapid brain cooling afforded by the transnasal technique provides superior protection compared to 24 hours of whole body surface cooling. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be used by emergency medical personnel and paramedics in the field and in both small and large hospital emergency rooms for early initiation of brain cooling prior to maintenance with standard surface cooling. It could eventually be deployed in low resource regions of the world, thereby having a transformative impact in expanding the efficacy and utilization of therapeutic hypothermia.

尽管最近院内儿科心脏骤停的出院率有所改善，但出院率仍居高不下。院外儿童心脏骤停的发生率和神经系统结果仍然很差。对于成人心脏逮捕患有缺氧缺血性脑病的受害者和新生儿，低温是唯一可用的方法治疗，尽管它不能为所有成人或新生儿提供完整的神经保护。对于出院小儿心脏骤停，最近的一项试验未能证明功能结果有所改善，部分原因是诱导低温延迟 5.9 小时。为了最大限度地减少这种延迟，我们开发了一种简单但创新的经鼻降温技术。环境温度下的干燥空气通过标准鼻插管，从口腔中流出，产生鼻道蒸发冷却和逆流热交换与头动脉血。一项正在进行的成人安全试验表明减少核心的可行性温度不会对鼻道产生不良影响。与人类相关的大型动物的试点数据与身体核心相比，幼儿和青少年的大脑冷却迅速、均匀且优先。窒息性心脏骤停新生动物模型的初步工作表明几乎完成了组织学研究早期开始经鼻冷却可保护神经元。然而，大脑冷却速度较慢新生儿和幼年动物比幼儿和幼年动物更常见，可能是因为鼻甲较小表面积和不发达的鼻毛细血管密度和血流量。为了更好地定义成熟效应，我们将研究两个年龄的动物在窒息心脏骤停和复苏后的经鼻冷却效果与婴儿和幼儿相关。这些年龄段的窒息逮捕发生率最高。在目标 1 中，我们将测量复苏后不同大脑区域和身体核心的冷却时间过程以评估可以冷却大脑而不会对肺部产生潜在不利影响的气流速率的有效范围循环。我们将确定大脑是否均匀冷却，与延迟皮层下冷却相反使用冷却头盔实现冷却。我们还将确定大脑是否比大脑冷却得更快身体核心。防止心脏过冷可以最大限度地降低心律失常的风险。在目标 2 中，我们将发起复苏后立即或两小时进行经鼻冷却，并高度量化神经元组织病理学脆弱的大脑区域，以确保在一系列临床相关延迟期间神经保护的功效。我们将确定经鼻技术提供的快速脑冷却是否提供卓越的保护与24小时全身表面冷却相比。由于它的简单性、便携性和低成本，经鼻冷却可能可供现场紧急医疗人员和护理人员使用在小型和大型医院急诊室中，在维护之前及早启动脑部冷却标准表面冷却。它最终可以部署在世界资源匮乏的地区，从而对扩大低温治疗的功效和利用产生变革性影响。