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

项目摘要 基本原理：大多数儿童急性呼吸窘迫综合征（PARDS），一种严重的肺 受伤需要机械通气在成人ARDS患者中， 死亡率，主要归因于新发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与 习俗和死亡率。NPMODS是死亡率的可行替代结局，PARDS的死亡率较低， 与机械通气损伤相关的生物相容性强， 识别儿童机械通气相关危害。在通过中介之前 结果NPMODS，由于大多数儿童在PARDS中存活，因此描述NPMODS与PARDS之间的关系至关重要。 NPMODS和ICU后发病率。研究：通过这个职业发展奖，Anoopindar Bhalla博士， 一位儿科重症监护医师，试图了解呼吸机管理，NPMODS和 重症监护病房后的发病率。该研究将利用基础设施和资源， 肺保护性通气策略的II期随机对照试验，入组276例PARDS儿童 由Bhalla博士的共同导师（PI：Khemani，NHLBI R 01 HL 134666，REDvent）领导。核心假设是 损伤性机械通气导致NPMODS，反过来，NPMODS与ICU后 PARDS患儿的发病率。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）确定生理性 PARDS中与NPMODS相关的有害通风机制（包括评估 3）描述NPMODS和ICU后发病率之间的关系 （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，增加职业发展培训活动， Bhalla博士将学习以下方面的关键技能：1）儿科临床试验的原则; 2） 先进的研究设计和生物统计学; 3）儿童ICU后结局的评估。获取这些 技能对于Bhalla博士的长期职业目标至关重要，即在重症儿童中领导设计良好的临床试验。 由呼吸生理学、生物统计学和长期研究领域的世界级专家组成的指导团队 结果以及临床试验，将支持她在这些努力。影响：这项研究将提供 关于损伤性机械通气、NPMODS和ICU术后相关性的重要信息 以指导未来的PARDS临床试验。此外，通过职业发展培训， 生成的数据，Bhalla博士将处于有利地位，成功地竞争R 01资金，并成为 领导儿科机械通气临床试验的独立研究者。

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.