Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial

儿科重症监护病房中的肾上腺素：剂量效应试验

• 批准号: 10649634
• 负责人: Catherine Ross
• 金额: $ 19.39万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649634
• 关键词: Acute; Address; Admission activity; Adopted; Adverse event; Affect; Age; American Heart Association; Awareness; Bioethics; Biometry; Blood Pressure; Bolus Infusion; Child; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Critical Care; Critical Illness; Data; Disclosure; Dose; Double-Blind Method; Education; Epinephrine; Event; Family; Frequencies; Funding; Future; General Population; Goals; Guidelines; Heart Arrest; Heart Diseases; Hematological Disease; Hospital Mortality; Hospitals; Hour; Hypertension; Hypotension; Informed Consent; Institution; Intensive Care Units; Intervention; Journals; Left; Lung diseases; Measures; Methods; Mission; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Neurologic; Observational Study; Outcome; Parents; Pathway interactions; Patients; Pediatric Intensive Care Units; Phase; Physicians; Population; Prevention; Public Health; Publications; Publishing; Qualitative Research; Randomized; Recommendation; Reporting; Research Personnel; Research Project Grants; Research Training; Resuscitation; Risk; Safety; Science; Standardization; Surveys; Survivors; Testing; Titrations; Training; United States; United States Food and Drug Administration; Visual; blood pressure elevation; career; clinical practice; design; disability; dosage; experience; hemodynamics; improved; medical schools; mortality; novel; pediatric patients; phase III trial; posters; prevent; prospective; risk minimization; secondary outcome; severe injury; social media; willingness

Pediatric in-hospital cardiac arrest is a highly lethal condition with nearly 60% mortality rate, and survivors are often left with neurologically devastating injuries which persist for a lifetime. Furthermore, prevention of cardiac arrest is inherent to the NHLBI's mission to “promote the prevention and treatment of heart, lung, and blood diseases”. Since pediatric in-hospital cardiac arrest is most commonly preceded by hypotension, its timely reversal and/or prevention may avert impending cardiac arrest. As a rapid bedside intervention, the clinical practice of administering bolus dilute epinephrine (BDE) for acute hypotension in the pediatric intensive care unit has emerged despite scant published evidence to support its use. As this practice is largely unstudied, optimal dosing of BDE in this population remains unclear. This project aims to determine if an initial dose of 0.5 mcg/kg versus 1 mcg/kg yields differences hemodynamic changes with the hypothesis that 1 mcg/kg will offer superior augmentation of blood pressure. To test this hypothesis, a Phase II, single-center, prospective, randomized, double-blind, dose-effect trial measuring systolic blood pressure before and after BDE is proposed. Pediatric patients in the intensive care unit with acute hypotension will be randomized to receive an initial dose of 0.5 mcg/kg versus 1 mcg/kg of BDE. Changes in systolic blood pressure following administration of BDE in the two groups will be compared. As a secondary outcome, the frequency of severe hypertension by age will be assessed. To inform the design of a future phase III trial, clinical outcomes such as need for subsequent doses, rates of subsequent cardiac arrest, adverse events and survival to discharge will also be explored. In addition to the primary clinical trial, a sub-study to develop and evaluate novel methods for public disclosure under the FDA-regulated Exception From Informed Consent will be performed. The candidate will pursue formal educational courses in qualitative research, bioethics, biostatistics and clinical trial design at the Harvard Schools of Medicine and Public Health. At the end of this training period, the candidate will be poised to meet her career goal of becoming an independent investigator in the field of pediatric resuscitation. She will have the data to support a larger trial funded through the R01 mechanism to address the overarching hypothesis that preemptive treatment of hypotension with a properly titrated dosage of epinephrine will prevent impending cardiac arrest. Furthermore, the candidate will have the key requisite experience in conducting future trials through Exception From Informed Consent to address challenging questions in pediatric resuscitation science that could not otherwise be answered.

儿科住院心脏骤停是一种高度致命的疾病，死亡率接近60%， 幸存者往往留下终生的神经上的毁灭性损伤。 此外，预防心脏骤停是NHLBI的使命所固有的，即“促进 心、肺、血液病的防治”。 由于小儿院内心脏骤停最常见的是低血压， 逆转和/或预防可以避免即将发生的心脏骤停。作为一种快速的床边干预， 大剂量稀释肾上腺素（BDE）治疗急性低血压的临床应用 儿科重症监护病房已经出现，尽管很少有公开的证据支持其使用。 由于这一做法基本上未经研究，因此该人群中溴化二苯醚的最佳剂量仍不清楚。 本项目旨在确定初始剂量0.5 mcg/kg与1 mcg/kg是否产生差异 假设1 mcg/kg将提供上级增强， 血压.为了检验这一假设，一项II期、单中心、前瞻性、随机、 双盲、剂量效应试验测量BDE前后的收缩压， 提出了重症监护室中患有急性低血压的儿科患者将被随机分组 初始剂量为0.5微克/千克，而非1微克/千克。收缩期血液变化 将比较两组中施用BDE后的压力。作为次要 结果，将按年龄评估严重高血压的频率。为设计提供信息 未来的III期试验，临床结果，如后续剂量的需要， 还将探讨随后的心脏骤停、不良事件和出院生存率。在 除了主要临床试验外，还进行了一项子研究，以开发和评估用于 将根据FDA规定的知情同意例外情况进行公开披露。 候选人将继续在定性研究，生物伦理学， 生物统计学和临床试验设计在哈佛医学院和公共卫生。在 培训结束后，候选人将准备好实现她的职业目标， 儿科复苏领域的独立调查员。她会有数据 支持通过R 01机制资助的更大规模的试验，以解决总体假设 预先用适当剂量的肾上腺素治疗低血压 防止即将发生的心脏骤停。此外，候选人将拥有关键的必要条件， 通过知情同意例外进行未来试验的经验， 儿科复苏科学中的挑战性问题，否则无法回答。

项目成果

Can an individual be enrolled in more than one clinical trial using exception from informed consent?

一个人可以使用知情同意例外的方式参加一项以上的临床试验吗？

• DOI: 10.1111/acem.14799
• 发表时间: 2024
• 期刊: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
• 作者: Ross,CatherineE;Asad,Muhammad;Kleinman,MonicaE;Donnino,MichaelW
• 通讯作者: Donnino,MichaelW

Peri-arrest bolus epinephrine practices amongst pediatric resuscitation experts.

• DOI: 10.1016/j.resplu.2021.100200
• 发表时间: 2022-03
• 期刊: Resuscitation plus
• 影响因子: 2.4
• 作者: Ross CE;Hayes MM;Kleinman ME;Donnino MW;Sullivan AM
• 通讯作者: Sullivan AM

Trends in Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study in the United States.

患有严重急性呼吸系统综合症冠状病毒 2 的危重儿童的疾病严重程度趋势：美国的一项回顾性多中心队列研究。

• DOI: 10.1097/pcc.0000000000003105
• 发表时间: 2023
• 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: Ross,CatherineE;Burns,JeffreyP;Grossestreuer,AnneV;Bhattarai,Pallav;McKiernan,ChristineA;Franks,JenniferD;Lehmann,Sonja;Sorcher,JillL;Sharron,MatthewP;Wai,Kitman;Al-Wahab,Haitham;Boukas,Konstantinos;Hall,MarkW;Ru,George

Characteristics and Outcomes of Cardiac Arrest in Adult Patients Admitted to Pediatric Services: A Descriptive Analysis of the American Heart Association's Get With The Guidelines-Resuscitation Data.

接受儿科服务的成年患者心脏骤停的特征和结果：对美国心脏协会的复苏指南数据的描述性分析。

• DOI: 10.1097/pcc.0000000000003104
• 发表时间: 2023
• 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: O'Halloran,AmandaJ;Grossestreuer,AnneV;Balaji,Lakshman;Ross,CatherineE;Holmberg,MathiasJ;Donnino,MichaelW;Kleinman,MonicaE;AmericanHeartAssociation’sGetWithTheGuidelines-ResuscitationInvestigators
• 通讯作者: AmericanHeartAssociation’sGetWithTheGuidelines-ResuscitationInvestigators

Community consultation in the pediatric intensive care unit for an exception from informed consent Trial: A survey of patient caregivers.

• DOI: 10.1016/j.resplu.2022.100355
• 发表时间: 2023-03
• 期刊: RESUSCITATION PLUS
• 影响因子: 2.4
• 作者: Ross, Catherine E.;Lehmann, Sonja;Hayes, Margaret M.;Yamin, Jolin B.;Berg, Robert A.;Kleinman, Monica E.;Donnino, Michael W.;Sullivan, Amy M.
• 通讯作者: Sullivan, Amy M.