Driving Pressure as a Target for Lung-Protective Ventilation

项目摘要/摘要 Sarina Sahetya，MHS医学博士，约翰霍普金斯大学肺部和重症监护内科科学家， 临床调查硕士学位。这份K23提案将为她提供宝贵的培训 长期的职业目标是成为一名独立的、由NIH资助的、以患者为导向的调查员 改善急性呼吸衰竭患者临床结局的随机试验。急性呼吸系统 窘迫综合征(ARDS)是一种常见且经常致命的急性呼吸衰竭类型，总体上 死亡率约40%。机械通气是ARDS治疗的基石。尽管它有拯救生命的作用， 机械通气还会导致呼吸机诱导的肺损伤(VILI)，这会增加发病率和 死亡率。最近，新冠肺炎疫情突显了最佳肺保护的重要性 改善患者预后的换气策略。最近的观察研究表明，将目标定为低 驾驶压力作为ARDS机械通风方法的一部分，可能会提高死亡率。这个K23 格兰特建立在Sahetya博士开发生理导引机械通气的先前经验的基础上 减少驾驶压力的方法。在这部K23中，她将前瞻性地评估驾驶压力- 肺保护性通气的导引途径。研究将在高度支持的情况下完成 在约翰霍普金斯大学的培训环境下，由一支具有相关专业知识的卓越导师团队指导。 这个K23奖项的总体目标是：(1)完成严格的多阶段试点工作，评估一个肺-- 最大限度减少ARDS患者驾驶压力的保护性通风策略，以及(2)培养基本技能 候选人要成为一名成功的独立的、以病人为中心的调查员。职业发展计划 将教学与高级统计分析关键领域的杰出导师相结合，严谨 通过定性方法优化方案和试验设计，并进行试点随机试验，以确保 向独立的成功过渡。使用最近参加NHLBI的ARDS患者的大型数据库- 资助的试验，Sahetya博士将评估驾驶压力变化之间的关系，由 呼气末正压和死亡率的变化，以及探讨患者的特征 这种关系(目标1)。她将用定性的方法深入了解临床医生的 优化通风RCT设计以完善拟议掘进压力的观点-- 引导式飞行员试验(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 礼宾(目标3)。这种严格的培训和有指导的研究经验将培养持续的生产力， 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.