Comparative safety and sedation effectiveness of intranasal dexmedetomidine versus midazolam for preoperative anxiety reduction in pediatric surgical patients: an updated systematic review and meta-analysis

BACKGROUND: Relieving pre-operative anxiety in children is a major concern for anesthesiologists. Midazolam has been the most commonly used sedative agent due to its long history of efficacy. However, it has been associated with complications, such as agitation, cognitive impairment, amnesia, and respiratory depression. For these reasons, other drugs, such as dexmedetomidine, have been explored as safe and effective alternatives in children undergoing surgery. OBJECTIVE: To evaluate the efficacy and safety of intranasal dexmedetomidine as compared to intranasal or oral midazolam in reducing preoperative anxiety in pediatric surgical patients. METHODS: PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant articles published from inception to January 2026. The search was limited to articles written in English and involved keywords and MeSH terms related to midazolam, dexmedetomidine, surgery, and children. RESULTS: Nineteen randomized controlled trials with 1475 pediatric surgical patients were included. The pooled analysis revealed that intranasal dexmedetomidine was associated with significantly lower anxiety scores at or before induction (SMD: -1.10; 95% CI: -1.68 to -0.53; p = 0.0002), parental separation anxiety (SMD: -0.56; 95% CI: -0.99 to -0.12; p = 0.01), and mean heart rate (HR) (MD: -6.60 beats/min; 95% CI: -10.56 to -2.64; p = 0.001) compared to intranasal midazolam. However, intranasal dexmedetomidine was comparable to oral midazolam in terms of anxiety at or before induction (MD: -7.70; 95% CI: -18.89 to 3.59; p = 0.18), parental separation anxiety (RR: 1.13; 95% CI: 0.44 to 2.88; p = 0.80), and postoperative emergence agitation (RR: 0.22; 95% CI: 0.02 to 2.94; p = 0.25). CONCLUSION: Intranasal dexmedetomidine is more effective than intranasal midazolam in reducing preoperative anxiety in children. No statistically significant difference was detected between intranasal dexmedetomidine and oral midazolam, but studies may have been underpowered to detect clinically important differences. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO: CRD420251234972.