Postoperative delirium (POD) is a frequent and serious complication among adult surgical patients, particularly older adults and those with cognitive vulnerability. Despite its prevalence, current prevention strategies remain inconsistent across surgical settings, creating a critical gap in perioperative care. Dexmedetomidine, an α2-adrenergic agonist with sedative and analgesic properties, has been increasingly studied for its potential to reduce POD through sympatholysis, sleep preservation, and reduced anesthetic requirements. This review followed the PRISMA-ScR guidelines. A systematic search of PubMed and the Cochrane Library identified studies published between January 2010 and January 2025. Eligible studies included randomized or pilot randomized controlled trials evaluating perioperative dexmedetomidine for prevention of postoperative delirium (POD) in adult surgical patients (≥18 years). Thirty trials met inclusion criteria. Data were systematically charted for study design, surgical population, dexmedetomidine dosing and timing, comparator strategies, delirium assessment methods, and reported safety outcomes, and were synthesized descriptively to map patterns across studies. The 30 trials included 6,630 patients across diverse surgical populations, including noncardiac major surgery, cardiac surgery, neurosurgery, thoracic procedures, hepatic surgery, orthopedic operations, and microvascular reconstruction. Across studies, dexmedetomidine was associated with reduced POD incidence in many trials, with the strongest signals observed in noncardiac major surgery, orthopedic procedures, and selected cardiac ICU sedation settings. Regimens demonstrating benefit most commonly used moderatedose continuous intraoperative infusion (0.2–0.7 µg/kg/h) or early postoperative sedation, whereas lowdose or intraoperative-only strategies frequently showed little to no effect. Hemodynamic effects, particularly hypotension and bradycardia, were common but generally manageable. Overall, dexmedetomidine shows promise as a perioperative strategy to reduce POD, especially in older or highrisk patients, but standardized protocols and targeted trials are needed to determine
