Duration of Hypothermia for Neuroprotection after Pediatric Cardiac Arrest

小儿心脏骤停后神经保护的低温持续时间

基本信息

批准号：
8447000
负责人：
ERICKA LINN FINK
金额：
$ 16.11万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8447000
关键词：
Adult Adverse event American Heart Association Animal Model Animals Apoptotic Area Asphyxia Attenuated Basal Ganglia Biochemical Biological Markers Birth Blood Circulation Brain Brain Hypoxia-Ischemia Brain Injuries Brain region Caring Cell Death Cessation of life Child Childhood Childhood Injury Choline Clinical Clinical Trials Design Coma Data Electrolytes Encephalopathies Environment Enzyme-Linked Immunosorbent Assay Etiology Event Experimental Models Family Foundations Frequencies Future Germ Cells Glasgow Coma Scale Goals Guidelines Heart Arrest Hour Human Incidence Induced Heart Arrest Infant Infection Intensive Care Units Ischemia Lead Life Magnetic Resonance Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Mentors Metabolism Methods Morbidity - disease rate N-acetylaspartate Necrosis Neonatal Nervous System Physiology Neurologic Neurological outcome Neuron-Specific Enolase Neurons Neuroprotective Agents North America Occipital lobe Outcome Pathway interactions Patient Recruitments Patients Pediatric Intensive Care Units Protons Public Health Quality of life Randomized Randomized Controlled Trials Reperfusion Therapy Research Research Personnel Research Proposals Resources Resuscitation Risk Serum Serum Proteins Sodium Sodium Lactate Spectrum Analysis Surrogate Markers Survival Rate Survivors Temperature Testing Thalamic structure Therapeutic Time Tissues Translating Traumatic Brain Injury Ventricular Fibrillation Work base brain metabolism clinical practice comparative efficacy design disability experience functional outcomes improved insight interest minimally invasive mortality natural hypothermia neonate neuron loss neuroprotection patient population prevent programs prospective response standard of care therapeutic target tool trend trial comparing

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY: Cardiac arrest (CA) in children is a significant public health problem that is associated with a survival rate of only 13%. About 50% of survivors sustain neurological disability, which produces an enormous impact on family life and resources. My research track record has focused on mechanisms of brain injury and therapies in experimental CA in the developing brain, which has prepared me to translate this work to the pediatric ICU. I have outstanding mentors, have developed relationships with expert researchers in other key area for this work, and have a superb research environment including the Safar Center for Resuscitation Research, the Magnetic Resonance Research Center, and a busy clinical pediatric ICU practice for patient recruitment. My short term research goal is to compare the efficacy of 24 h versus 72 h of mild hypothermia (HT) (32-34 9C) in children with CA as a neuroprotective strategy. There isnot neuroprotective therapy for CA in children, where the etiology is primarily asphyxia. Randomized controlled trials using mild HT with varying durations in adult ventricular fibrillation-induced CA (12-24 h) and neonatal asphyxia (72 h) significantly improved neurological outcome without increasing adverse events. However, there are no prospective data on the use of HT in children with CA. Our experience shows substantial secondary neuronal death beyond 24 h after CA in children (as reflected by peak serum levels of the neuronal death biomarker neuron specific enolase [NSE]). Thus, prolonging the duration of HT from 24 h to 72 h may further attenuate secondary neuronal death. Serum biomarkers such as NSEand brain magnetic resonance spectroscopy (MRS) are minimally invasive methods used to evaluate the brain's biochemical response to CA and therapies such as HT. I propose to prospectively randomize 40 children with CA to either 24 h or 72 h of mild HT to test the hypothesis that treatment with mild HT for 72 h will be superior to 24 h as evidenced by the reduction of biochemical evidence of brain injury. Specific aims are designed to find the best duration of HT that shows evidence of neurological protection, as measured biochemically using serum NSE and brain MRS concentrations of N-acetyl aspartate, lactate and sodium. In addition, the frequency of adverse events will be compared between the two groups. The long- term aim of this proposal is to serve as the scientific foundation for optimized clinical trials designed to improve neurological outcome and quality of life in children who survive CA. RELEVANCE: Cardiac arrest in children has a survival rate of only 13%, and half of the survivors have neurological disability. There are currently no therapies to improve survival and neurological function in children with cardiac arrest. The impact of cardiac arrest for families is significant in terms of effects on family life and financially, since care for a child surviving cardiac arrest can amount to one million dollars over a lifetime.

描述（由申请人提供）：项目摘要：儿童心脏骤停 (CA) 是一个重大的公共卫生问题，其存活率仅为 13%。大约 50% 的幸存者患有神经系统残疾，这对家庭生活和资源产生巨大影响。我的研究记录主要集中在发育中大脑的实验性 CA 的脑损伤机制和治疗方法，这为我将这项工作转化为儿科 ICU 做好了准备。我拥有出色的导师，与其他关键领域的专家研究人员建立了合作关系，并拥有一流的研究环境，包括萨法尔复苏研究中心、磁共振研究中心以及繁忙的临床儿科 ICU 患者招募实践。我的短期研究目标是比较 24 小时与 72 小时亚低温 (HT) (32-34 9C) 作为神经保护策略对 CA 儿童的疗效。儿童 CA 没有神经保护疗法，其病因主要是窒息。使用不同持续时间的轻度 HT 治疗成人心室颤动引起的 CA（12-24 小时）和新生儿窒息（72 小时）的随机对照试验显着改善了神经系统结果，且不增加不良事件。然而，没有关于 HT 在 CA 儿童中使用的前瞻性数据。我们的经验表明，儿童 CA 后 24 小时后出现大量继发性神经元死亡（如神经元死亡生物标志物神经元特异性烯醇化酶 [NSE] 的血清峰值水平所反映）。因此，将 HT 持续时间从 24 小时延长至 72 小时可能会进一步减轻继发性神经元死亡。 NSE 和脑磁共振波谱 (MRS) 等血清生物标志物是微创方法，用于评估大脑对 CA 和 HT 等疗法的生化反应。我建议前瞻性地将 40 名 CA 儿童随机分为 24 小时或 72 小时轻度 HT 治疗，以检验以下假设：72 小时轻度 HT 治疗优于 24 小时，脑损伤生化证据的减少证明了这一点。具体目标是找到显示神经保护证据的 HT 最佳持续时间，使用血清 NSE 和脑 MRS 浓度的 N-乙酰天冬氨酸、乳酸盐和钠进行生化测量。此外，还将比较两组之间不良事件的发生频率。该提案的长期目标是为优化临床试验提供科学基础，旨在改善 CA 存活儿童的神经系统结果和生活质量。相关性：儿童心脏骤停的存活率仅为 13%，并且一半的幸存者患有神经功能障碍。目前尚无治疗方法可以改善心脏骤停儿童的生存率和神经功能。心脏骤停对家庭的影响在家庭生活和经济方面都非常重要，因为心脏骤停幸存的孩子一生的护理费用可能高达一百万美元。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Physical and occupational therapy utilization in a pediatric intensive care unit.

儿科重症监护病房中物理和职业治疗的应用。

DOI：
发表时间：
2017
期刊：
影响因子：
3.7
作者：
Cui, Liang R;LaPorte, Megan;Civitello, Matthew;Stanger, Meg;Orringer, Maxine;Casey 3rd, Frank;Kuch, Bradley A;Beers, Sue R;Valenta, Cynthia A;Kochanek, Patrick M;Houtrow, Amy J;Fink, Ericka L
通讯作者：
Fink, Ericka L

Global and Regional Derangements of Cerebral Blood Flow and Diffusion Magnetic Resonance Imaging after Pediatric Cardiac Arrest.

小儿心脏骤停后脑血流和弥散磁共振成像的整体和区域紊乱。

DOI：
发表时间：
2016-02
期刊：
影响因子：
0
作者：
Manchester, Leah C;Lee, Vince;Schmithorst, Vincent;Kochanek, Patrick M;Panigrahy, Ashok;Fink, Ericka L
通讯作者：
Fink, Ericka L

International Survey of Critically Ill Children With Acute Neurologic Insults: The Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment Study.

患有急性神经系统损害的危重儿童的国际调查：儿童急性危重神经系统疾病的患病率：全球流行病学评估研究。

DOI：
发表时间：
2017-04
期刊：
影响因子：
0
作者：
Fink, Ericka L;Kochanek, Patrick M;Tasker, Robert C;Beca, John;Bell, Michael J;Clark, Robert S B;Hutchison, Jamie;Vavilala, Monica S;Fabio, Anthony;Angus, Derek C;Watson, R Scott;Prevalence of Acute critical Neurological disease in children: A
通讯作者：
Prevalence of Acute critical Neurological disease in children: A

Serum biomarkers of brain injury: a call for collaboration*.

脑损伤的血清生物标志物：呼吁合作*。

DOI：
发表时间：
2014-09
期刊：
影响因子：
0
作者：
Trakas, Erin V;Fink, Ericka L
通讯作者：
Fink, Ericka L

Interfacility Transport Shock Index Is Associated With Decreased Survival in Children.

设施间运输冲击指数与儿童存活率下降有关。

DOI：
发表时间：
2019-10
期刊：
影响因子：
1.4
作者：
Jennings, Ryan M;Kuch, Bradley A;Felmet, Kathryn A;Orr, Richard A;Carcillo, Joseph A;Fink, Ericka L
通讯作者：
Fink, Ericka L