Purpose. The purpose of this dissertation is to understand the state of recommended practice for sedation interruptions (SI) and to discover factors that hinder or facilitate critical care nurses’ use in practice. To garner insight about why this evidence-informed intervention is not being used as recommended to improve mechanically ventilated patient outcomes. Methods. A series of studies using a multi-methods design and guided by the Knowledge to Action Framework: study 1) a systematic review and critical appraisal examined the quality and reporting of all available guidelines and care bundles with recommendations related to SI for mechanically ventilated adults in critical care; study 2) a needs assessment included an environmental scan of the study site and gap-analysis using a retrospective chart audit to measure the nature and magnitude of the evidence-practice gap; study 3) a descriptive qualitative study used semi-structured theory-based interviews to deepen our understanding of the determinants that influence SI use in preparation for a future implementation study. Findings. Study 1 included 11 guidelines and care bundles with 15 recommendations about SI. Deficiencies in the methodological quality of the current guidelines and care bundles may impact overall credibility and applicability of the recommendations, though SI is currently recommended best-practice. Study 2 confirmed the existence of an evidence-practice gap related to SI and affirmed the need to discover barriers and drivers to best practice implementation (study 3). We identified nine facilitators and 20 barriers to SI use by nurses. Facilitators were associated with the innovation (e.g., the importance of protocols) and the potential adopters (e.g., SI are specific to the nurse's role). The barriers were associated with the potential adopters (e.g., nurses’ knowledge gaps and variable goals of SI) and the practice environment (e.g., lack of availability of extra staff and multidisciplinary rounds). Conclusion. Before adequately implementing SI and evaluating uptake by nurses, we need to address modifications to existing guidelines and recommendations, even though SI is considered best practice. A theory-informed implementation study can further activate the use of SI for mechanically ventilated adults in critical care.