Driving Pressure as a Target for Lung-Protective Ventilation

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.