Optimal Ventilator Management in Patients with ARDS on ECMO

PROJECT SUMMARY/ABSTRACT Research Plan: Acute respiratory distress syndrome (ARDS) is a severe and common condition that affects 10% of patients in the intensive care unit (ICU), and was a major cause of morbidity and mortality during the COVID-19 pandemic. While mechanical ventilation is often necessary for ARDS, it can also induce additional lung injury known as ventilator induced lung injury (VILI). VILI may be minimized by using low tidal volumes/driving pressure and with positive end expiratory pressure (PEEP). Some patients with severe and refractory ARDS require veno-venous extracorporeal membrane oxygenation (V-V ECMO), the highest level of life support which provides oxygen and removes carbon dioxide from the blood using an external device. A major benefit of ECMO is thought to be the ability to minimize VILI; however, the optimal ventilator settings for patients with ARDS on ECMO are not known. Current guidelines use a one-size-fits-all approach. Our central hypothesis is that personalized PEEP adjusted by measuring intrathoracic pressures via esophageal manometry (Pes) will decease VILI as assessed by biomarkers of inflammation (main outcomes IL-6 and sRAGE). To carry out these aims, we plan to prospectively randomize 62 patients with ARDS on V-V ECMO and neuromuscular blockade and perform serial biomarker measurements with PEEP of 10 cmH2O (ECMO guidelines) vs. PEEP guided by esophageal manometry. In addition to biomarkers of VILI, we will assess differences in other physiological outcomes including pulmonary mechanics and gas exchange. Although this proposal focuses on patients on ECMO, we believe the knowledge gained will have relevance for all patients with ARDS. Career Development Plan: The goal of the PI, Dr. Mazen Odish, is to personalize ARDS and ventilator strategies for those on ECMO based on physiology and biomarkers. The PI has an interest in applied physiology and critical care, this award will help him refine these skills and develop new skills in clinical trials, statistics, and patient-oriented research, to test rigorously methods to care for critically ill patients with ARDS with or without ECMO. To obtain these new skills Dr. Odish and his excellent and multi-disciplinary mentoring/advisory team (led by Drs. Owens and Malhotra, plus outstanding statistical and methodologic support) has three main training goals. 1) Pulmonary mechanics and biomarkers during ARDS, 2) control of breathing and measurement of work of breathing during ARDS/mechanical ventilation, and 3) clinical trial design and statistical training. These training activities are tailored for the PI to achieve his goals and maximize career development towards becoming an independent physician scientist. Furthermore, his structured course work will lead to a Masters of Advanced Studies in Clinical Research. Dr. Odish is at the right place and time in his career to align his clinical expertise in ECMO and ARDS with his research goals to understand optimal ventilator settings and therapies. Eventually his work and new skill set may improve the lives of all people suffering from respiratory illness.