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: 9087348
• 负责人: Alexis A. Topjian
• 金额: $ 17.46万
• 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 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9087348
• 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; Hypoxic-Ischemic Brain Injury; Impact Seizures; Injury; Institution; Intravenous; Investigation; 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; improved outcome; member; mortality; novel; novel strategies; patient oriented; professor; statistics; success; survival outcome; 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) 和费城儿童医院 (CHOP) 麻醉、重症监护和儿科助理教授 Alexis Ann Topjian 博士正在重新提交指导患者的申请-面向研究职业发展奖（K23）。作为一名儿科重症监护研究员和早期 CCM 教员，这位候选人的工作重点是发展成为一名以患者为中心的神经科学家。本申请中拟议的调查是她在被捕后神经科学方面不断增长的经验和专业知识的自然发展。 Topjian 博士的近期目标是评估一种新方法，用于实时 ICU 床边癫痫发作检测，并及时处理心脏骤停后危重儿童的非惊厥性癫痫发作。她的长期职业目标是改善小儿心脏骤停后的神经系统结果和生活质量。她渴望成为一名独立的神经科学家，专注于复苏后护理。环境：职业发展计划和预期的研究调查建立在候选人所在机构现有的研究和指导网络的基础上。该候选人与她的导师在儿科重症监护病房实施了每天 24 小时/每周 7 天的神经监测系统，这将作为进行她的研究的基础。她将继续在宾夕法尼亚大学临床流行病学和生物统计学中心学习流行病学和高级统计学课程。她拥有丰富的统计资源来完成该项目并开展未来的研究调查。这种环境与专家指导团队的结合几乎保证了她的成功，因为她成长为一名独立的复苏神经科学家。研究：每年有超过 8,000 名儿童发生心脏骤停，导致高死亡率和神经系统发病率。在自主循环恢复后的前 3 天内，这些儿童中几乎一半患有非惊厥性癫痫发作 (NCS)，其中 2/3 患有非惊厥性癫痫持续状态 (NCSE)。由于缺乏严格的监测或及时的脑电图解释，NCS 和 NCSE 的识别和治疗可能会被延迟（或者直到进展到临床可检测的体征和症状时才被检测到或治疗）。重要的是，延长 NCS 和静脉注射抗惊厥药物治疗 NCS 可能会引起不良反应，最终恶化生存和/或神经系统结果。 这项具体研究的目的是评估一种实时 ICU 床边 NCS 检测的新方法，并促进心脏骤停后危重儿童的 NCS 管理。 目标 1 将评估 连续脑电图模式、密度谱阵列 (DSA) 的诊断准确性（敏感性、特异性、阳性和阴性预测值），供床边 ICU 医生和护士实时检测 NCS。目标 2 将通过将患者随机分配至 DSA 监测或标准 EEG 监测，评估与标准 EEG 监测和治疗相比，使用 DSA 监测和及时治疗对心脏骤停后儿童非惊厥性癫痫发作的有效性和安全性。主要疗效结果是：1) 检测、2) 治疗和 3) 终止 NCS 的时间。不良后果的主要衡量标准是低血压的强度和持续时间。最后，在目标 3 中，我们将评估在控制损伤严重程度后，逮捕后前三天内较大的 NCS 负担是否与逮捕后 6 个月时更差的神经系统结果相关。摘要：本次以患者为导向的研究职业发展奖申请中的计划将提供杰出的早期职业经验、优越的环境和世界一流的指导，帮助候选人为成为一名独立研究者做好准备。此外，这些目标的成功实现将为未来的研究奠定基础，以确定非惊厥性癫痫发作的实时诊断和及时治疗是否可以减少心脏骤停后危重儿童的短期和长期神经损伤。

项目成果

Neuroprognostication after pediatric cardiac arrest.

小儿心脏骤停后的神经预测。

• 发表时间: 2014-11
• 影响因子: 3.8
• 作者: Kirschen, Matthew P;Topjian, Alexis A;Hammond, Rachel;Illes, Judy;Abend, Nicholas S
• 通讯作者: Abend, Nicholas S

Cardiopulmonary resuscitation for in-hospital events in the emergency department: A comparison of adult and pediatric outcomes and care processes.

急诊科院内事件的心肺复苏：成人和儿童结果和护理过程的比较。

• 发表时间: 2015-07
• 影响因子: 6.5
• 作者: Donoghue, Aaron J;Abella, Benjamin S;Merchant, Raina;Praestgaard, Amy;Topjian, Alexis;Berg, Robert;Nadkarni, Vinay;American Heart Association's Get With the Guidelines
• 通讯作者: American Heart Association's Get With the Guidelines

Brain resuscitation in the drowning victim.

对溺水者进行脑复苏。

• 发表时间: 2012-12
• 影响因子: 3.5
• 作者: Topjian, Alexis A;Berg, Robert A;Bierens, Joost J L M;Branche, Christine M;Clark, Robert S;Friberg, Hans;Hoedemaekers, Cornelia W E;Holzer, Michael;Katz, Laurence M;Knape, Johannes T A;Kochanek, Patrick M;Nadkarni, Vinay;van der Hoeven, Johann
• 通讯作者: van der Hoeven, Johann

High frequency oscillation and airway pressure release ventilation in pediatric respiratory failure.

高频振荡和气道压力释放通气治疗小儿呼吸衰竭。

• 发表时间: 2014-07
• 影响因子: 3.1
• 作者: Yehya, Nadir;Topjian, Alexis A;Lin, Richard;Berg, Robert A;Thomas, Neal J;Friess, Stuart H
• 通讯作者: Friess, Stuart H

The authors reply.

作者回复。

• 发表时间: 2015-02
• 作者: Topjian, Alexis A;Friess, Stuart H
• 通讯作者: Friess, Stuart H