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

儿科住院心脏骤停是一种高致命性疾病，死亡率接近60%， 幸存者往往会受到神经上毁灭性的伤害，这种伤害会持续终生。 此外，防止心脏骤停是NHLBI的使命所固有的，其使命是“促进 防治心、肺、血液病“。 由于儿科住院期间心脏骤停最常见的症状是低血压，因此及时 逆转和/或预防可避免即将发生的心脏骤停。作为一种快速的床边干预， 静脉推注稀释肾上腺素治疗急性低血压的临床应用 尽管几乎没有公开发表的证据支持儿科重症监护病房的使用，但它还是出现了。 由于这种做法在很大程度上没有被研究，因此在这一人群中BDE的最佳剂量仍然不清楚。 该项目旨在确定初始剂量为0.5微克/公斤与1微克/公斤是否会产生差异 血流动力学变化假设1微克/公斤将提供更好的增强 血压。为了检验这一假设，第二阶段，单中心，前瞻性，随机， BDE前后测量收缩压的双盲剂量效应试验 建议。重症监护病房中急性低血压的儿科患者将被随机分组 接受0.5微克/公斤的初始剂量，而不是1微克/公斤的BDE。收缩压血的变化 比较两组BDE给药后的压力。作为次要角色 结果，将评估按年龄划分的严重高血压的频率。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， 随后的心脏骤停、不良事件和出院后的存活率也将被探讨。在……里面 除了主要的临床试验外，还进行了一项子研究，以开发和评估治疗 将根据FDA规定的知情同意例外情况进行公开披露。 应聘者将继续攻读定性研究、生物伦理学、 哈佛大学医学院和公共卫生学院的生物统计学和临床试验设计。在… 本次培训结束后，应聘者将准备实现她的职业目标，成为 儿科复苏领域的独立研究员。她将拥有数据来 支持通过R01机制资助的更大规模的试验，以解决总体假设 使用适当剂量的肾上腺素对低血压进行预防性治疗将 防止即将发生的心脏骤停。此外，候选人将拥有关键的必备条件 通过知情同意例外进行未来试验的经验 儿科复苏科学中具有挑战性的问题，否则无法得到回答。

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.