Efficacy and Safety of Ketamine-Dexmedetomidine Combination in Adult Sedation and Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

This project is a systematic review and meta-analysis aimed at evaluating the safety and efficacy of the ketamine-dexmedetomidine combination (often referred to as “Ketodex”) in adult patients undergoing sedation or general anesthesia. Ketodex has gained attention due to the potential synergistic effects of its components—ketamine, an NMDA receptor antagonist with analgesic and dissociative properties, and dexmedetomidine, a highly selective alpha-2 adrenergic agonist with sedative and sympatholytic effects. The review will focus on outcomes such as hemodynamic stability (heart rate and blood pressure), respiratory parameters (e.g., oxygen saturation), depth of sedation (measured by validated scales such as BIS or RASS), time to recovery, and adverse events. Both randomized controlled trials (RCTs) and high-quality non-randomized studies involving adult populations will be considered. A comprehensive search will be conducted across major databases, including PubMed, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. Additional strategies such as citation tracking, reference list screening, and searching thesis/dissertation databases will be used to identify relevant studies. The review will adhere to PRISMA 2020 guidelines. Risk of bias will be assessed using RoB 2 (for RCTs) and ROBINS-I (for non-randomized studies). Meta-analyses will be conducted using random-effects models, and the certainty of evidence will be rated using the GRADE framework. The expected outcome is to provide evidence-based conclusions on whether the Ketodex combination offers superior clinical outcomes compared to other sedative or anesthetic strategies in adults. The findings may inform future clinical guidelines and practice in anesthesiology and critical care.