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)：亚历克西斯·安·托普健博士，宾夕法尼亚大学(UPenn)和费城儿童医院(CHOP)麻醉、危重护理和儿科助理教授，正在重新提交她的导师以患者为导向的研究职业发展奖(K23)的申请。这位候选人作为儿科重症监护研究员和早期CCM教员，致力于发展成为一名以患者为中心的神经科学家。这项申请中的拟议调查是她在逮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。托普金博士的近期目标是评估一种新的方法，用于实时检测ICU床边发作，并迅速处理心脏骤停后危重儿童的非惊厥性发作。她的长期职业目标是改善儿科心脏骤停后的神经学结果和生活质量。她渴望成为一名独立的神经学家，专注于复苏后的护理。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。这位候选人和她的导师已经在儿科重症监护病房实施了一套每周7天、每天24小时的神经监测系统，这将成为她进行研究的基础。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。她拥有丰富的统计资源来完成这个项目并开展未来的研究调查。这种环境和一个专家指导团队的结合几乎保证了她在发展成为一名独立的复苏神经科学家时取得成功。研究：每年有8000多名儿童心脏骤停，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，几乎一半的儿童有非惊厥性癫痫发作(NCS)，其中2/3的儿童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解释，NCS和NCSE的识别和治疗可能会延迟(或者直到进展到临床可检测到的体征和症状才能发现或治疗)。重要的是，延长NCS和静脉注射抗惊厥药物治疗NCS都可能导致不良反应，最终恶化存活率和/或神经预后。这项具体研究的目的是评估一种新的方法，用于实时检测ICU床边NCS，并在危重儿童心脏骤停后迅速进行NCS处理。目标1将评估 用于床边ICU医生和护士实时检测NCS的连续脑电设备密度谱阵列(DSA)的诊断准确性(灵敏度、特异度、阳性和阴性预测值)。目的2通过将患儿随机分为DSA监测和标准脑电监测，评价DSA监测和快速治疗与标准EEG监测和治疗对儿童心脏骤停后非惊厥发作的疗效和安全性。主要的疗效结果将是：1)检测、2)治疗和3)终止NCS的时间。衡量不良结果的主要指标是低血压的强度和持续时间。最后，在目标3中，我们将评估在控制了损伤严重程度后，在停药后前三天内较大的NCS负荷是否与停药后6个月的神经学结果较差相关。摘要：本次以患者为导向的导师研究职业发展奖申请中的计划将提供出色的早期职业经验、优越的环境和世界级的指导，为候选人成为一名独立调查人员做好准备。此外，这些目标的成功实现将为未来的研究奠定基础，以确定非惊厥性发作的实时诊断和及时治疗是否可以减少危重儿童心脏骤停后的短期和长期神经损伤。

项目成果

Treatment of electrographic seizures and status epilepticus in critically ill children: a single center experience.

• DOI: 10.1016/j.seizure.2013.03.008
• 发表时间: 2013-07
• 期刊: SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
• 影响因子: 3
• 作者: Abend, Nicholas S.;Sanchez, Sarah M.;Berg, Robert A.;Dlugos, Dennis J.;Topjian, Alexis A.
• 通讯作者: Topjian, Alexis A.

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

• DOI: 10.1002/ppul.22853
• 发表时间: 2014-07
• 期刊: PEDIATRIC PULMONOLOGY
• 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.

Survival Rates Following Pediatric In-Hospital Cardiac Arrests During Nights and Weekends.

• DOI: 10.1001/jamapediatrics.2016.2535
• 发表时间: 2017-01-01
• 期刊: JAMA pediatrics
• 影响因子: 26.1
• 作者: Bhanji F;Topjian AA;Nadkarni VM;Praestgaard AH;Hunt EA;Cheng A;Meaney PA;Berg RA;American Heart Association’s Get With the Guidelines–Resuscitation Investigators
• 通讯作者: American Heart Association’s Get With the Guidelines–Resuscitation Investigators

Women of child-bearing age have better inhospital cardiac arrest survival outcomes than do equal-aged men.

育龄的妇女比同龄男人更好的室内心脏骤停生存结果。

• DOI: 10.1097/ccm.0b013e3181d8ca43
• 发表时间: 2010-05
• 期刊: Critical care medicine
• 影响因子: 8.8
• 作者: Topjian AA;Localio AR;Berg RA;Alessandrini EA;Meaney PA;Pepe PE;Larkin GL;Peberdy MA;Becker LB;Nadkarni VM;American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators
• 通讯作者: American Heart Association National Registry of Cardiopulmonary Resuscitation Investigators

Seizure Detection by Critical Care Providers Using Amplitude-Integrated Electroencephalography and Color Density Spectral Array in Pediatric Cardiac Arrest Patients.

• DOI: 10.1097/pcc.0000000000001099
• 发表时间: 2017-04
• 期刊: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
• 作者: Du Pont-Thibodeau G;Sanchez SM;Jawad AF;Nadkarni VM;Berg RA;Abend NS;Topjian AA
• 通讯作者: Topjian AA