Effects of Dexmedetomidine–Remifentanil on Neurodevelopment of Children after Inhalation Anesthesia: A Randomized Clinical Trial

Background: Anesthetic exposure in young children raises concerns about neurodevelopmental safety, with preclinical evidence suggesting potential neurotoxicity of volatile anesthetics. This study aimed to assess whether the combination of dexmedetomidine and remifentanil, by reducing sevoflurane exposure, has any differential effect on neurodevelopmental outcomes in young children compared with sevoflurane alone. Methods: This study was a prospective, double-blind, randomized clinical trial including children younger than 2 yr undergoing nonstaged, nonrepetitive surgeries. Participants received dexmedetomidine and remifentanil as adjuncts to sevoflurane (DEX-R group) or sevoflurane alone (control group). The study assessed their neurodevelopmental status at 28 to 30 months using the Korean Leiter International Performance Scale and the Child Behavior Checklist, as predefined secondary outcomes. The primary endpoint—full-scale IQ at 5 yr of age—will be reported after completion of long-term follow-up. Results: Among 400 enrolled participants, 343 completed assessments (169 control, 176 DEX-R). There was no difference in the mean anesthesia duration between the control and DEX-R groups (77.1 min vs. 72.8 min; mean difference [95% CI], 4.4 [−3.8 to 12.6]; P = 0.293). The mean end-tidal sevoflurane concentration was significantly lower in the DEX-R group than in the control group (1.8 vol% vs . 2.6 vol%; mean difference [95% CI], −0.9 [−1.0 to −0.7] vol%; P < 0.001). The mean full-scale IQ score was 102.5 ± 11.5 in the DEX-R group and 103.6 ± 11.5 in the control group (mean difference, −1.1; 95% CI, −3.9 to 1.7; P = 0.442). No significant difference was observed in the Child Behavior Checklist total score between groups. Conclusions: The addition of dexmedetomidine and remifentanil to sevoflurane anesthesia was not associated with significant differences in neurodevelopmental outcomes at 28 to 30 months compared to sevoflurane alone.