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: 10216068
• 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/10216068
• 关键词: Acute respiratory failure; Adoption; Adult; Adult Respiratory Distress Syndrome; Artificial Respiration; Automobile Driving; Award; Biological; Biometry; Breathing; Cessation of life; Chest wall structure; Child; Childhood; Clinical Trials; Clinical Trials Design; Communities; 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; base; career; career development; design; follow-up; functional status; health related quality of life; improved; lung injury; mortality; multidisciplinary; novel; novel strategies; pressure; prevent; primary outcome; randomized trial; respiratory; secondary analysis; secondary outcome; shear stress; 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.

项目摘要 理由：大多数儿童急性呼吸窘迫综合征（PARS）的儿童，一种严重的肺形式 在患有ARDS的成年人中，受伤的机械通气实践增加了 死亡率，主要归因于新或进行性多器官功能障碍综合征的发展 （npmods）。小儿研究没有发现机械通气之间的类似一致的关联 实践和死亡率。 NPMODS是死亡率的可行替代结果，帕德的死亡率很低， 具有强大的生物学合理性，可与有害机械通气相关，并可能改善 鉴定机械通气与儿童相关的危害。在采用中级之前 结果NPMods，因为大多数儿童都在帕德斯幸存下 NPMOD和ICU后发病率。研究：通过这个职业发展奖，Anoopindar Bhalla博士， 小儿浓缩主义者试图了解呼吸机管理，NPMOD和 帕德儿童的ICU后发病率。该研究将利用A的基础设施和资源 II期关于肺部保护策略的随机对照试验，招收了276名患有帕克的儿童 并由Bhalla博士的副主管（PI：Khemani，NHLBI R01 HL134666，Redvent）领导。中心假设是 这种有害的机械通气导致NPMODS，而NPMods又与ICU有关 儿童的发病率。这些假设将通过以下特定目的进行检验：1） 确定肺部保护策略是否阻止了PARS中的NPMOD； 2）识别生理学 有害通风的机制与PARS中的NPMOD相关（包括评估 转肺压力）； 3）表征NPMODS与ICU后发病率之间的关联 （与健康相关的生活质量，功能状况和肺状况）。职业发展： 通过完成拟议的研究，其他职业发展培训活动以及 多学科指导，巴拉博士将在1）儿科临床试验原理中学习关键技能； 2） 高级研究设计和生物统计学； 3）评估儿童后ICU结果。获取这些 技能对于Bhalla博士的长期职业目标至关重要，即领导重症儿童精心设计的临床试验。 由世界一流的呼吸生理学，生物统计学和长期的世界一流的专家组成的精通团队 结果和临床试验将在这些努力中支持她。影响：这项研究将提供 关于有害机械通气，NPMOD和ICU之间关联的关键信息 发病率指导未来的PARS临床试验。此外，通过职业发展培训和 生成的数据，Bhalla博士将有充分的位置，以成功争夺R01资金并成为 独立研究者领先的小儿机械通气临床试验。