The Effects of Preoperative Intranasal Administration of Dexmedetomidine and Esketamine on Negative Postoperative Behavioral Changes in Children With Autism Spectrum Disorder

This study is a multicenter, prospective, randomized, double-blind, controlled clinical trial designed to evaluate the effects of preoperative intranasal sedation on negative postoperative behavioral changes (NPOBCs) in children with autism spectrum disorder (ASD) undergoing elective surgery under general anesthesia Children with ASD often experience heightened perioperative anxiety, sensory sensitivity, and difficulty adapting to unfamiliar medical environments. These factors place them at increased risk for NPOBCs, which may include emotional distress, irritability, sleep disturbances, fear-related behaviors, and reduced cooperation with medical care after surgery. Effective and well-tolerated preoperative sedation may help reduce perioperative stress responses and improve postoperative behavioral outcomes. However, high-quality evidence in children with ASD remains limited.

This study will enroll a total of 234 participants across multiple pediatric hospitals. Participants will be randomly assigned in a 1:1:1 ratio to one of three intervention groups: intranasal dexmedetomidine, intranasal esketamine, or intranasal saline as a control. Randomization will be centrally managed using a stratified block design to balance study center, age group, and surgical category. Blinding will be maintained for participants, caregivers, anesthesiologists, outcome assessors, and data analysts to minimize bias.

Study medication will be administered intranasally approximately thirty minutes before anesthesia induction using identical, unlabeled nasal spray devices. All participants will then receive routine general anesthesia and perioperative management according to standard clinical practice at each participating center. The surgical procedure and anesthetic technique will not be altered by study participation.

The primary objective of the study is to compare the incidence of NPOBCs seven days after surgery among the three groups. Behavioral outcomes will be assessed using validated caregiver-reported questionnaires appropriate for children with ASD. Secondary objectives include evaluating behavioral changes at three and twenty-eight days after surgery, emergence agitation during recovery, postoperative pain, quality of preoperative sedation, and overall safety.

In addition to clinical and behavioral assessments, electroencephalographic (EEG) data will be collected during the emergence period from anesthesia. These data will be analyzed to explore potential associations between neurophysiological patterns and subsequent behavioral outcomes. This exploratory component aims to support the development of predictive models for postoperative behavioral risk in children with ASD.

Participant safety is a key priority. All adverse events will be systematically recorded and reviewed in accordance with Good Clinical Practice guidelines. Serious adverse events will be reported promptly and reviewed by an independent data and safety monitoring process. Ongoing safety oversight will include regular review of adverse event rates across study centers.

The study is expected to provide clinically relevant evidence on whether intranasal dexmedetomidine or intranasal esketamine administered before anesthesia can reduce postoperative behavioral disturbances in children with ASD. Findings from this trial may help inform future perioperative management strategies and support more individualized, evidence-based care for this vulnerable population.

• Incidence of negative postoperative behavioral changes (NPOBCs) at postoperative day 1 and postoperative day 30, assessed using the Post Hospitalization Behavior Questionnaire for Autism Spectrum Disorder (PHBQ-AS). [Срок оценки: Postoperative day 3 and postoperative day 28]