PROJECT SUMMARY/ABSTRACT Annually in the United States, approximately 250,000 patients require mechanical ventilation in the emergency department (ED) and over 30% will die. The majority of survivors experience crippling long-term disability including cognitive decline, psychological dysfunction, and lengthy rehabilitation. Recent data suggest that exposure to deep sedation (i.e. unconsciousness or coma due to excessive sedative administration) after the initiation of mechanical ventilation is associated with greater mechanical ventilation duration, lengths of stay, and mortality. Deep sedation is extremely common while mechanical ventilation is provided in the ED; however, no clinical study has tested if targeting light sedation in the immediate post-intubation period in the ED improves outcome. Our hypothesis is that targeting a light sedation depth after the initiation of mechanical ventilation in the ED is associated with improved clinical outcomes, including a reduced duration of mechanical ventilation. To test this hypothesis, our team will capitalize on our extensive experience with initiating clinical studies in the ED and continuing these intervention protocols into the intensive care unit (ICU), and will propose a future multi-center, stepped-wedge, cluster randomized trial. The scientific literature and our preliminary data provide the rationale for conducting a large-scale clinical trial. However, several gaps currently prohibit proceeding. The feasibility of implementing an ED-based goal- oriented sedation protocol is unknown in terms of: 1) recruitment; 2) efficacy in achieving target sedation; 3) reliability of sedation measurements during routine care in the ED; 4) adverse events; and 5) barriers to implementation. Therefore this proposal is for a multicenter (n= 3) prospective before-and-after protocol implementation study examining the feasibility of a protocol which targets light sedation after intubation among 344 mechanically ventilated adult ED patients. These data will be supplemented with a qualitative assessment of barriers to implementation (survey of nurses and physicians). Through the aims of this preparatory pilot study, we will acquire the necessary and sufficient data, and demonstrate a clear organizational structure, critical to complete the full-scale clinical trial. This project has the potential to completely change the clinical practice of early sedation management, and improve survival and quality of life in patients suffering from acute respiratory failure. Given the magnitude of death and disability experienced by mechanically ventilated ED patients, even modest improvements would provide a major public health benefit.