Project Summary Despite the lifesaving nature of mechanical ventilation, it is associated with complications such as ventilator- induced lung injury, ventilator-associated events, ventilator induced diaphragm dysfunction and exposure to narcotic and sedative medications. Minimizing the length of exposure to mechanical ventilation is therefore a goal of intensive care practitioners, which must be balanced against premature termination of mechanical ventilation which can lead to additional complications. Unfortunately, there is a high degree of variability in ventilator management practices, particularly when it comes to reducing ventilator support and assessing whether a pediatric patient is ready for liberation from mechanical ventilation. While there is some pediatric evidence to guide clinical practice, there are inconsistencies between many of these studies, which may relate to different operational definitions and methods surrounding extubation readiness and extubation failure. While there have been some excellent physiologic, observational, and even randomized controlled trials on aspects of pediatric ventilator liberation, robust research data is lacking. Given the lack of data in many areas, a standard approach and process of systematic review is unlikely to yield enough evidence to guide practice. Our central hypothesis is that an innovative, hybrid approach which combines systematic review with consensus opinion of international experts can generate high-quality recommendations to guide clinical practice and highlight important areas for future research. The main goal of this project is to establish guidelines, informed by clinical evidence, for the definitions and process of evaluating pediatric patients for extubation readiness, and establish priorities for future research. To achieve this goal, we propose a 2 year project period which includes 2 in-person meetings of a diverse, international panel of approximately 25 multi-disciplinary experts in pediatric mechanical ventilation. We will use the modified Convergence of Opinion on Recommendations and Evidence (CORE) methodology which is a novel approach to speed up systematic reviews and is well validated against the traditional Institute of Medicine approach. The methods will involve refinement of key “P.I.C.O” questions through a series of tele- conferences, voting on recommendations, systematic review, presentation of findings at in-person meetings, generation of the consensus-based recommendations for dissemination, and identification of key knowledge gaps for future research. This project can have an immediate impact on the lives of critically ill children by providing best practice guidelines to decrease duration of mechanical ventilation and extubation failure and their associated short- and long-term morbidities.