Prompt Diagnosis and Treatment of Subclinical Seizures After Cardiac Arrest

心脏骤停后亚临床癫痫发作的及时诊断和治疗

• 批准号: 8882563
• 负责人: Alexis A. Topjian
• 金额: $ 17.62万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882563
• 关键词: Adverse effects; Adverse event; Anesthesia procedures; Anticonvulsants; Behavioral; Biometry; Blood Circulation; Brain Injuries; Caring; Categories; Cerebrum; Child; Childhood; Critical Care; Critically ill children; Detection; Development Plans; Diagnosis; Early identification; Early treatment; Environment; Epidemiology; Epilepsy; Faculty; Foundations; Future; Goals; Heart Arrest; Hour; Hypotension; Impact Seizures; Injury; Institution; Intravenous; Investigation; Ischemic-Hypoxic Encephalopathy; Lactic Acidosis; Location; Measurable; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modality; Monitor; Morbidity - disease rate; Motor Seizures; Neurologic; Neurological outcome; Neurosciences; Non-Convulsive Status Epilepticus; Nurses; Outcome; Patients; Pattern; Pediatric Hospitals; Pediatric Intensive Care Units; Pediatrics; Pennsylvania; Performance; Pharmaceutical Preparations; Philadelphia; Physicians; Pilot Projects; Predictive Value; Provider; Quality of life; Randomized; Reading; Research; Research Personnel; Resources; Resuscitation; Safety; Seizures; Sensitivity and Specificity; Severities; Signs and Symptoms; Status Epilepticus; Subclinical Seizures; Supportive care; Survivors; System; Time; Training; Universities; adverse outcome; career; career development; clinical epidemiology; density; diagnostic accuracy; experience; group intervention; improved; member; mortality; novel; novel strategies; patient oriented; professor; statistics; success; tool

DESCRIPTION (provided by applicant): Dr. Alexis Ann Topjian, Assistant Professor of Anesthesia, Critical Care, and Pediatrics at the University of Pennsylvania (UPenn), and the Children's Hospital of Philadelphia (CHOP), is resubmitting her application for the Mentored Patient-Oriented Research Career Development Award (K23). This candidate has focused her efforts as a Pediatric Critical Care Fellow and early CCM faculty member on developing into a patient-oriented neuroscientist. The proposed investigation in this application is a natural progression of her growing experience and expertise in post-arrest neuroscience. Dr. Topjian's immediate goal is to evaluate a novel approach for real-time ICU bedside seizure detection and prompt management of non-convulsive seizures in critically ill children following cardiac arrest. Her long-term career goal is to improve neurologic outcomes and quality of life following pediatric cardiac arrest utilizing. She aspires to become an independent neuroscientist focusing on post-resuscitation care. Environment: The career development plan and the intended research investigation build upon an existing network of research and mentorship already in place at the candidate's institution. The candidate with her mentors has implemented a 24 hour per day/7 days per week Neuro-monitoring system in the pediatric intensive care unit which will serve as the foundation for performing her research. She will continue her coursework at UPenn's Center for Clinical Epidemiology and Biostatistics focusing on epidemiology and advanced statistics. She has extensive statistical resources to complete this project and develop future research investigations. The combination of this environment paired with an expert mentorship team all but guarantees her success as she develops into an independent resuscitation neuroscientist. Research: More than 8,000 children suffer a cardiac arrest each year, resulting in high mortality and neurologic morbidity. During the first 3 days following retur of spontaneous circulation, almost half of these children have non-convulsive seizures (NCS), of whom 2/3 have non-convulsive status epileptics (NCSE). NCS and NCSE identification and treatment may be delayed (or not detected or treated until progression to clinically detectable signs and symptoms) because of lack of rigorous monitoring or timely EEG interpretation. Importantly, both prolonged NCS and intravenous anticonvulsant medications to treat NCS may cause adverse effects, ultimately worsening survival and/or neurologic outcomes. The goal of this specific study is to evaluate a novel approach for real-time ICU bedside NCS detection and prompt NCS management in critically ill children following cardiac arrest. Aim 1 will evaluate the diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of a continuous EEG modality, Density Spectral Array (DSA), for the real-time detection of NCS by bedside ICU physicians and nurses. Aim 2 will evaluate the efficacy and safety of using DSA monitoring and prompt treatment compared with standard EEG monitoring and treatment for non-convulsive seizures in children post-cardiac arrest by randomizing patients to DSA monitoring or standard EEG monitoring. The primary efficacy outcomes will be time to: 1) detection, 2) treatment and 3) termination of NCS. The primary measure of adverse outcome is the intensity and duration of hypotension. Finally, in Aim 3 we will evaluate if larger NCS burden during the first three days post-arrest is associated with worse neurologic outcome at 6 months post-arrest after controlling for severity of injury. Summary: The plan in this Mentored Patient-Oriented Research Career Development Award application will provide the outstanding early career experience, superior environment and world-class mentorship to prepare the candidate to become an independent investigator. In addition, successful accomplishment of these aims will provide the foundation for future investigations to determine if real-time diagnosis and prompt treatment of non-convulsive seizures can decrease short- and long-term neurologic injury for critically ill children post- cardiac arrest.

描述（由申请人提供）：宾夕法尼亚大学（UPENN）的麻醉，重症监护和儿科助理教授Alexis Ann Topjian博士以及费城儿童医院（CHOP）正在重新启用她的受过指导患者注重患者的研究职业发展奖（K23）的申请。这位候选人将她作为儿科重症监护室和早期CCM教职员工的努力集中在发展为患者的神经科学家。该应用程序中拟议的调查是她不断增长的经验和逮捕后神经科学专业知识的自然发展。 Topjian博士的近期目标是评估一种新颖的方法，用于实时ICU床边癫痫发作检测，并迅速管理心脏骤停后重症儿童中的非脱惊厥性癫痫发作。她的长期职业目标是改善使用儿科心脏骤停后的神经系统成果和生活质量。她渴望成为专注于震荡后护理的独立神经科学家。环境：职业发展计划和预期的研究调查建立在候选人机构已经建立的现有研究和指导网络的基础上。与她的导师的候选人每天在儿科重症监护室实施每天24小时/7天的神经监测系统，这将是进行研究的基础。她将继续在UPENN的临床流行病学和生物统计学中心，重点是流行病学和高级统计。她拥有广泛的统计资源来完成该项目并进行未来的研究调查。这种环境与专家指导团队的结合几乎保证了她发展成为独立复苏神经科学家的成功。研究：每年有8,000多名儿童遭受心脏骤停，导致死亡率高和神经系统发病。在自发循环恢复后的前3天内，这些儿童中几乎有一半的癫痫发作（NCS），其中2/3具有非阻驱状态癫痫病（NCSE）。由于缺乏严格的监测或及时的脑电图解释，NCS和NCSE识别和治疗可能会延迟（或直到临床可检测到临床可检测到的体征和症状）。重要的是，长时间的NC和静脉注射抗惊厥药治疗NCS可能会引起不良反应，最终使生存率和/或神经系统结局恶化。 这项具体研究的目的是评估一种新型的ICU床旁NCS检测方法，并促使心脏骤停后重症儿童的NCS管理。 AIM 1将评估 连续的EEG模式，密度光谱阵列（DSA）的诊断精度（灵敏度，特异性，正和负预测值），用于通过床边ICU医生和护士实时检测NCS。 AIM 2将通过将患者随机将DSA监测或标准脑电图监测的患者随机使患者随机使患者后患者的非震颤性癫痫发作与标准的脑电图监测和治疗相比，评估使用DSA监测和及时治疗的功效和安全性。主要功效结果将是：1）检测，2）治疗和3）NCS的终止。不利预后的主要度量是低血压的强度和持续时间。最后，在AIM 3中，我们将评估在控制后6个月后，在逮捕后的头三天，较大的NCS负担是否与较差的神经系统结局有关。摘要：这项受过指导的以患者为导向的研究职业发展奖的计划将提供出色的早期职业经验，卓越的环境和世界一流的指导，以准备候选人成为独立研究者。此外，这些目标的成功实现将为将来的研究提供基础，以确定实时诊断和迅速治疗非扰动性癫痫发作是否会减少心脏骤停后重症儿童的短期和长期神经损伤。