Intranasal Dexmedetomidine or Esketamine for Negative Postoperative Behavioral Changes in Children

This multicenter, prospective, randomized, double-blind, controlled clinical trial will evaluate whether preoperative intranasal dexmedetomidine or esketamine can reduce negative postoperative behavioral changes in children undergoing day surgery under general anesthesia. The study will also explore whether perioperative electroencephalographic (EEG) features are associated with these behavioral changes and may help explain the effects of the study drugs.

A total of 342 children undergoing elective day surgery will be enrolled across four centers. Eligible participants will be randomly assigned in a 1:1:1 ratio to receive intranasal dexmedetomidine 2.0 micrograms/kg, intranasal esketamine 1.0 mg/kg, or an equal volume of normal saline approximately 30 minutes before induction of anesthesia. Study medications will be prepared in identical, unlabeled nasal spray devices to maintain blinding. Participants, investigators, and outcome assessors will remain unaware of treatment assignment throughout the study.

After study drug administration, participants will undergo routine perioperative monitoring. Sedation will be assessed before surgery. During anesthesia and recovery, EEG and other perioperative clinical data will be collected. Postoperative assessments will include pain and emergence delirium. Negative postoperative behavioral changes will be evaluated on postoperative days 3, 7, and 28. The primary outcome is the incidence of negative postoperative behavioral changes on postoperative day 7. Secondary analyses will assess behavioral outcomes at postoperative days 3 and 28 and examine the relationship between perioperative EEG patterns and postoperative behavioral changes.

This study is designed to provide evidence on the comparative effects of intranasal dexmedetomidine and esketamine on postoperative behavioral recovery in children undergoing day surgery and to identify perioperative EEG markers that may be associated with adverse behavioral outcomes.

Inclusion criteria

• Children aged 2 to 12 years.
• Scheduled to undergo elective day surgery under general anesthesia.
• ASA (American Society of Anesthesiologists) physical status I to III.

Exclusion criteria

• Congenital diseases or severe liver or kidney dysfunction.
• History of allergic reactions to study drugs.
• Neuromuscular diseases, cerebral palsy, epilepsy.
• Other psychiatric or neurological disorders.
• Body mass index (BMI) ≥ 30 kg/m².
• Severe upper respiratory tract infections prior to surgery.
• Use of sedatives or analgesics within 48 hours before surgery.
• Exposure to major life stressors within 1 month before surgery (e.g., family separation, death of a parent).
• Refusal to participate or failure to obtain consent from the child's legal guardian.