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.

尽管最近有医院儿科心脏骤停的住院率有所提高，但出院院外小儿心脏骤停的率和神经系统效果仍然很差。对于成人心脏逮捕受害者和新生儿患有缺氧 - 缺血性脑病，体温过低是唯一可用的治疗，尽管它没有在所有成年人或新生儿中提供完整的神经保护作用。用于院外儿科心脏骤停，最近的一项试验未能证明功能结果改善，部分原因是 5.9小时诱导体温过低。为了最大程度地减少这种延迟，我们开发了一个简单而创新的跨纳萨冷却技术。在环境温度下干燥的空气通过标准的鼻套管和从口腔中产生鼻通道和反电流交换的蒸发冷却带有头血动脉血。成人正在进行的安全试验表明，降低核心的可行性温度对鼻腔没有不利影响。与人有关的大型动物的飞行员数据与人体核心相比，幼儿和少年表明快速，均匀和优先的大脑冷却。在新生动物的沥青心脏骤停模型中的初步工作表明几乎完整的组织学神经元保护，并早期开始经鼻的冷却。但是，大脑冷却的速度较慢新生儿和婴儿动物比在幼儿和少年动物中，可能是由于鼻涡板较小表面积和不发达的鼻毛细管密度和血液流动。为了更好地定义成熟效应，我们将研究两个年龄段的动物的沥青心脏骤停和复苏后的经纳纳萨尔冷却功效与婴儿和幼儿有关。这些年龄组的沥青逮捕发生率最高。在AIM 1中，我们在复苏后，将测量不同大脑区域和身体核心的时间过程以评估气流速率的有效范围可以冷却大脑，而不会对肺部产生潜在的不利影响循环。我们将确定大脑是否均匀冷却，与延迟皮层相比带有冷却头盔的冷却。我们还将确定大脑是否比身体核心。预防过冷的心脏应最大程度地减少心律不齐的风险。在AIM 2中，我们将启动复苏后立即或两个小时的跨inasal冷却，并在高度量化神经元组织病理学脆弱的大脑区域可确保神经保护在一系列临床相关延迟中的功效。我们将确定经鼻技术提供的快速脑冷却是否提供了优越的保护相比之下，全身表面冷却24小时。由于其简单性，可移植性和低成本，跨inasal冷却可能会在现场紧急医务人员和护理人员使用，以及在小型和大型医院急诊室中，在维护之前，请尽早开始大脑冷却标准表面冷却。它最终可以部署在世界低资源区域中，从而在扩大治疗性体温过低的功效和利用方面的变革性影响。