Driving Pressure as a Target for Lung-Protective Ventilation

项目总结/摘要 萨里纳Sahetya，医学博士MHS是约翰霍普金斯大学的肺部和重症监护医生科学家， 临床研究硕士学位。这个K23提案将为她提供宝贵的培训， 作为一个独立的长期职业目标，NIH资助，以病人为导向的研究人员进行 旨在改善急性呼吸衰竭患者临床结局的随机试验。急性呼吸 窘迫综合征（ARDS）是一种常见的、经常致命的急性呼吸衰竭类型， 死亡率约40%。机械通气是ARDS治疗的基石。尽管有救命的效果， 机械通气也可引起呼吸机诱导的肺损伤（VILI），这可增加发病率， mortality.最近，COVID-19大流行凸显了最佳肺部保护的重要性 改善患者预后的通气策略。最近的观察性研究表明， 驱动压力作为ARDS机械通气方法的一部分，可以改善死亡率。K23 格兰特建立在Sahetya博士先前开发生理引导机械通气的经验基础上 减少驾驶压力的方法。在这个K23中，她将前瞻性地评估一个驱动压力- 肺保护性通气的引导方法。该研究将在高度支持的 在约翰霍普金斯的培训环境中，在具有相关专业知识的优秀导师团队的指导下， K23奖的总体目标是：（1）完成严格的多阶段试点工作，评估肺- 保护性通气策略，最大限度地减少ARDS患者的驱动压力;（2）培养基本技能 候选人是一个成功的独立的以病人为导向的研究者。职业发展计划 结合教学法，在先进的统计分析，严谨的关键领域杰出的导师， 通过定性方法优化方案和试验设计，并进行初步随机试验，以确保 成功过渡到独立。使用最近NHLBI中登记的ARDS患者的大型数据库， Sahetya博士将评估驾驶压力变化之间的关系， 呼气末正压和死亡率的变化，并探索改变患者特征的 这一关系（目标1）。她将使用定性方法深入了解临床医生的 优化通风RCT设计的观点，以完善建议的驱动压力- 引导试点试验（目标2）。最后，她将进行一项试点随机对照试验，评估 驱动压力引导通气策略与ARDS网络肺保护通气策略的比较 方案（目标3）。这种严格的培训和指导研究经验将促进持续的生产力， 为未来的NIH R级拨款提供初步数据，并为职业生涯奠定坚实的基础 开展新干预措施的临床试验，以改善急性呼吸衰竭患者的预后。

PROJECT SUMMARY/ABSTRACT Sarina Sahetya, MD MHS is a pulmonary and critical care physician-scientist at Johns Hopkins University, with a Master’s degree in Clinical Investigation. This K23 proposal will provide her valuable training towards her long-term career goal of being an independent, NIH-funded, patient-oriented investigator conducting randomized trials to improve clinical outcomes for patients with acute respiratory failure. Acute respiratory distress syndrome (ARDS) is a common and frequently fatal type of acute respiratory failure with an overall mortality ~40%. Mechanical ventilation is a cornerstone of ARDS management. Despite its life-saving effect, mechanical ventilation also can cause ventilator-induced lung injury (VILI), which can increase morbidity and mortality. Recently, the COVID-19 pandemic has highlighted the importance of optimal lung-protective ventilation strategies to improve patient outcomes. Recent observational studies suggest that targeting low Driving Pressure, as part of a mechanical ventilation approach for ARDS, could improve mortality. This K23 grant builds on Dr. Sahetya’s prior experience with developing physiologically-guided mechanical ventilation approaches for reducing Driving Pressure. In this K23, she will prospectively evaluate a Driving Pressure- guided approach to lung-protective ventilation. The research will be completed within the highly supportive training environment at Johns Hopkins, with the guidance of a team of superb mentors with relevant expertise. The overall objectives of this K23 Award are to: (1) complete rigorous multi-phase pilot work evaluating a lung- protective ventilation strategy minimizing Driving Pressure for ARDS patients, and (2) develop essential skills for the candidate to be a successful independent patient-oriented investigator. The career development plan combines didactics, with outstanding mentorship in key areas of advanced statistical analysis, rigorous protocol and trial design optimization via qualitative methods, and conduct of a pilot randomized trial, to ensure a successful transition to independence. Using a large database of ARDS patients enrolled in a recent NHLBI- funded trial, Dr. Sahetya will evaluate the relationship between changes in Driving Pressure, arising from changes in positive end-expiratory pressure, and mortality as well as explore patient characteristics that modify this relationship (Aim 1). She will use qualitative methods to gain in-depth understanding of clinicians’ perspectives on optimizing the design of ventilation RCTs in order to refine a proposed Driving Pressure- guided pilot trial (Aim 2). Finally, she will conduct a pilot randomized controlled trial evaluating the feasibility of a Driving Pressure-guided ventilation strategy compared to the ARDS Network lung-protective ventilation protocol (Aim 3). This rigorous training and mentored research experience will foster continued productivity, provide preliminary data for a future NIH R-level grant, and establish a strong foundation for a career conducting clinical trials of new interventions to improve patient outcomes in acute respiratory failure.