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: 10468178
• 负责人: Catherine Ross
• 金额: $ 19.29万
• 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/10468178
• 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; Dose-Rate; Double-Blind Method; 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; Lead; 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; Savings; Science; Standardization; Surveys; Survivors; Testing; Time; 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%