Mechanical Ventilation Management, New or Progressive MODS, and Post-ICU Morbidity in Pediatric ARDS

机械通气管理、新发或进行性 MODS 以及儿科 ARDS 的 ICU 后发病率

• 批准号: 10596094
• 负责人: Anoopindar Bhalla
• 金额: $ 17.5万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596094
• 关键词: Acute Respiratory Distress Syndrome; Acute respiratory failure; Adoption; Adult; Artificial Respiration; Automobile Driving; Award; Biological; Biometry; Breathing; Cessation of life; Chest wall structure; Child; Childhood; Clinical Trials; Clinical Trials Design; Community Healthcare; Coupled; Critical Care; Critical Illness; Critically ill children; Data; Development; Diagnosis; Enrollment; Esophagus; Family; Funding; Future; Goals; Guidelines; Infrastructure; Intensive Care Units; Intervention; K-Series Research Career Programs; Lead; Learning; Lung; Manometry; Measures; Mechanical ventilation; Mentors; Mentorship; Morbidity - disease rate; Multiple Organ Failure; Muscular Atrophy; National Heart, Lung, and Blood Institute; Organ failure; Outcome; Outcomes Research; Patients; Pediatric Acute Respiratory Distress Syndrome; Phase; Physiological; Positioning Attribute; Positive-Pressure Respiration; Protocols documentation; Randomized; Randomized, Controlled Trials; Recovery; Research; Research Design; Research Personnel; Resources; Respiratory physiology; Sample Size; Statistical Data Interpretation; Survivors; Testing; Tidal Volume; Time; Training; Training Activity; United States; Ventilator; atelectrauma; career; career development; design; follow-up; functional status; health related quality of life; improved; lung injury; lung pressure; mortality; multidisciplinary; novel; novel strategies; pressure; prevent; primary outcome; randomized trial; respiratory; secondary analysis; secondary outcome; shear stress; skill acquisition; skills; standard care; ventilation

PROJECT SUMMARY Rationale: Most children with pediatric acute respiratory distress syndrome (PARDS), a severe form of lung injury, require mechanical ventilation. In adults with ARDS, injurious mechanical ventilation practices increase mortality, primarily attributed to the development of new or progressive multiple organ dysfunction syndrome (NPMODS). Pediatric studies have not found similar consistent associations between mechanical ventilation practices and mortality. NPMODS is a feasible alternative outcome to mortality, which is low in PARDS, that has strong biological plausibility for association with injurious mechanical ventilation and may improve identification of mechanical ventilation associated harm in children. Before adoption of the intermediary outcome NPMODS, as most children survive PARDS, it is crucial to characterize the association between NPMODS and post-ICU morbidity. Research: Through this career development award, Dr. Anoopindar Bhalla, a pediatric intensivist, seeks to understand the associations between ventilator management, NPMODS, and post-ICU morbidity in children with PARDS. The research will leverage the infrastructure and resources of a Phase II randomized controlled trial on a lung-protective ventilation strategy enrolling 276 children with PARDS and led by Dr. Bhalla’s co-mentor (PI: Khemani, NHLBI R01 HL134666, REDvent). The central hypothesis is that injurious mechanical ventilation leads to NPMODS and, in turn, NPMODS is associated with post-ICU morbidity in children with PARDS. These hypotheses will be tested through the following Specific Aims: 1) Determine whether a lung-protective ventilation strategy prevents NPMODS in PARDS; 2) Identify physiologic mechanisms of injurious ventilation which are associated with NPMODS in PARDS (including assessment of transpulmonary pressures); 3) Characterize the association between NPMODS and post-ICU morbidity (health-related quality of life, functional status, and pulmonary status) in PARDS. Career Development: Through completion of the proposed research, additional career development training activities, and multidisciplinary mentorship, Dr. Bhalla will learn key skills in 1) the principles of pediatric clinical trials; 2) advanced study design and biostatistics; 3) the assessment of post-ICU outcomes in children. Acquiring these skills is critical for Dr. Bhalla’s long-term career goal to lead well-designed clinical trials in critically ill children. The assembled mentorship team with world-class experts in respiratory physiology, biostatistics, and long-term outcomes as well as clinical trials, will support her in these endeavors. Impact: This research will provide crucial information on the associations between injurious mechanical ventilation, NPMODS, and post-ICU morbidity to guide future PARDS clinical trials. Furthermore, through the career development training and generated data, Dr. Bhalla will be well-positioned to successfully compete for R01 funding and become an independent investigator leading pediatric mechanical ventilation clinical trials.

项目概要 理由：大多数儿童患有小儿急性呼吸窘迫综合征 (PARDS)，这是一种严重的肺部疾病 受伤，需要机械通气。在患有 ARDS 的成人中，有害的机械通气做法增加 死亡率，主要归因于新的或进行性多器官功能障碍综合征的发生 （NPMODS）。儿科研究尚未发现机械通气之间存在类似的一致关联 实践和死亡率。 NPMODS 是死亡率的一种可行的替代结果，PARDS 的死亡率较低， 与有害的机械通气相关具有很强的生物学合理性，并且可能会改善 识别机械通气对儿童的相关危害。在采用中介之前 结果 NPMODS，由于大多数儿童都能幸存 PARDS，因此表征之间的关联至关重要 NPMODS 和 ICU 后发病率。研究：通过这项职业发展奖，Anoopindar Bhalla 博士， 一名儿科重症监护医师，致力于了解呼吸机管理、NPMODS 和 PARDS 儿童的 ICU 后发病率。该研究将利用以下机构的基础设施和资源： 肺保护性通气策略的 II 期随机对照试验，招募了 276 名 PARDS 儿童 由 Bhalla 博士的联合导师（PI：Khemani、NHLBI R01 HL134666、REDvent）领导。中心假设是 有害的机械通气会导致 NPMODS，而 NPMODS 又与 ICU 术后相关 PARDS 儿童的发病率。这些假设将通过以下具体目标进行检验：1) 确定肺保护性通气策略是否可以预防 PARDS 中的 NPMODS； 2）识别生理 与 PARDS 中的 NPMODS 相关的有害通气机制（包括评估 跨肺压）； 3) 描述 NPMODS 与 ICU 后发病率之间的关联 （PARDS 中与健康相关的生活质量、功能状态和肺部状态）。职业发展： 通过完成拟议的研究、额外的职业发展培训活动，以及 在多学科指导下，Bhalla 博士将学习以下方面的关键技能：1）儿科临床试验的原理； 2） 高级研究设计和生物统计学； 3）评估儿童ICU后的结局。获得这些 巴拉博士领导精心设计的危重儿童临床试验的长期职业目标至关重要。 由呼吸生理学、生物统计学和长期研究领域世界级专家组成的导师团队 结果以及临床试验将支持她的这些努力。影响：这项研究将提供 关于有害机械通气、NPMODS 和 ICU 术后之间关联的重要信息 发病率来指导未来的 PARDS 临床试验。此外，通过职业发展培训和 生成的数据，Bhalla 博士将处于有利地位，能够成功竞争 R01 资金并成为 领导儿科机械通气临床试验的独立研究者。