Date: December 2o, 2024 Reference: Kotani et al. Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review. Crit Care. 2023  Guest Skeptic: Dr. Scott Weingart is an ED Intensivist from New York. He did fellowships in Trauma, Surgical Critical Care, and ECMO. He is a physician coach concentrating on the promotion of eudaimonia and optimal performance. Scott is best known for talking to himself about Resuscitation and Critical Care on a podcast called EMCrit, which has been downloaded more than 50 million times.   Case: A 40-year-old male presents to the emergency department (ED) with severe respiratory failure from bilateral pneumonia. After a trial of Non-Invasive Positive Pressure Ventilation (NIPPV), you’ve decided to intubate him. Should your first pass attempt be done with a bougie or a styletted tube? Randomization Background: The role of single-center randomized controlled trials (sRCTs) in advancing medical knowledge is significant, especially in the field of emergency medicine (EM). These trials often serve as the initial foundation for exploring interventions, providing a focused and controlled environment to test hypotheses. However, the applicability of their findings to broader clinical settings can be limited due to their localized context. Multi-center randomized controlled trials (mRCTs) are often seen as a necessary step to validate these findings across diverse patient populations and healthcare settings. This process of validation is critical, as it addresses external validity—a cornerstone of evidence-based practice​​. Historically, the need to move from sRCTs to mRCTs arises from the recognition that different institutions have varied patient demographics, resources, and protocols that might influence outcomes. While sRCTs provide essential insights, their ability to reflect real-world complexities is inherently restricted​​. Emergency physicians, who operate in unpredictable environments, often rely on evidence that is robust across multiple settings to guide clinical decisions effectively. Despite the apparent hierarchical superiority of mRCTs, there are debates about whether they consistently confirm the results of sRCTs. This discussion is pivotal in understanding how findings can be generalized and integrated into clinical guidelines​​. As emergency physicians, evaluating the interplay between sRCTs and mRCTs not only helps in assessing the reliability of evidence but also in shaping the way we approach the implementation of interventions in our practice. Clinical Question: How often are single-centred RCTs of critically ill patients reporting a mortality benefit confirmed in a multi-centred RCT? Reference: Kotani et al. Positive single-center randomized trials and subsequent multicenter randomized trials in critically ill patients: a systematic review. Crit Care. 2023  Population: sRCTs published in high-impact journals (NEJM, JAMA, or Lancet) that reported statistically significant mortality reductions in critically ill patients. Exclusions: Quasi-randomized or non-randomized methodologies, multicentric trials, pediatric populations, and studies lacking mortality data. Intervention: sRCTs Comparison: mRCTs Outcome: Primary Outcome: Mortality assessed at specified time points such as hospital discharge or predefined follow-up periods. Secondary Outcomes: Guideline utilization of sRCT results, subsequent guideline changes based on mRCT Type of Study: Systematic review that followed the PRISMA guidelines and was registered in the PROSPERO International Prospective Register of Systematic Reviews Authors’ Conclusions: “Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines.” Quality Checklist for Systematic Reviews: