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

NCT ID: NCT07324057

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 234 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-01
• Study Completion Date: 2027-11-30

Brief Summary

The goal of this clinical trial is to learn whether intranasal sedation given before anesthesia can lower negative postoperative behavioral changes in children with autism spectrum disorder who undergo elective surgery. The study will compare two commonly used sedative medicines with a saline control. It will also examine the safety of these medicines and explore how brain electrical activity during recovery may relate to later behavior changes.

The main questions this study aims to answer are:

• Does intranasal dexmedetomidine given before anesthesia lower negative postoperative behavioral changes seven days after surgery in children with autism spectrum disorder?

• Does intranasal esketamine given before anesthesia lower negative postoperative behavioral changes seven days after surgery in children with autism spectrum disorder?

• Are there differences in postoperative agitation, pain, and sedation quality among the three groups? Researchers will compare dexmedetomidine, esketamine, and saline to see whether either medicine works better than saline in reducing postoperative behavior changes.

Participants will:

• Be randomly assigned to receive intranasal dexmedetomidine, intranasal esketamine, or intranasal saline about thirty minutes before anesthesia

• Undergo their planned surgery with standard general anesthesia care ③ Be assessed for behavior changes at three, seven, and twenty-eight days after surgery ④ Have routine monitoring of recovery, pain, agitation, and safety outcomes during and after surgery

Detailed Description

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.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine Intranasal Spray (D Group)

Participants assigned to the Dexmedetomidine Intranasal Spray receive dexmedetomidine at a dose of 2 micrograms per kilogram (maximum 100 micrograms), diluted to 1 milliliter and administered intranasally approximately 30 minutes before anesthesia induction.

Group Type: EXPERIMENTAL

Intranasal dexmedetomidine

Intervention Type: DRUG

Dosage: 2.0 µg/kg (maximum 100 µg) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To provide sedation, reduce preoperative anxiety, and potentially prevent postoperative behavioral issues like agitation and delirium.

Esketamine Intranasal Spray (L Group)

Participants receive esketamine 1 milligram per kilogram (maximum 50 milligrams), diluted to 1 milliliter and administered intranasally approximately 30 minutes before anesthesia induction.

Group Type: EXPERIMENTAL

Intranasal Esketamine

Intervention Type: DRUG

Dosage: 1.0 mg/kg (maximum 50 mg) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To provide sedation, reduce anxiety, and minimize postoperative behavioral changes like aggression and agitation.

Saline Control Group (C Group)

Participants receive normal saline 1 milliliter administered intranasally approximately 30 minutes before anesthesia induction.

Group Type: PLACEBO_COMPARATOR

saline control

Intervention Type: DRUG

Dosage: Equal volume of saline (1 ml) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To serve as a placebo control, allowing comparison to the active intervention groups.

Interventions

Intranasal dexmedetomidine

Dosage: 2.0 µg/kg (maximum 100 µg) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To provide sedation, reduce preoperative anxiety, and potentially prevent postoperative behavioral issues like agitation and delirium.

Intervention Type: DRUG

Intranasal Esketamine

Dosage: 1.0 mg/kg (maximum 50 mg) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To provide sedation, reduce anxiety, and minimize postoperative behavioral changes like aggression and agitation.

Intervention Type: DRUG

saline control

Dosage: Equal volume of saline (1 ml) Administration: Intranasal spray, 30 minutes before anesthesia induction Purpose: To serve as a placebo control, allowing comparison to the active intervention groups.

Intervention Type: DRUG

Other Intervention Names

· Dexmedetomidine nasal spray · Intranasal dexmedetomidine · Dexmedetomidine intranasal spray · Dexmedetomidine intranasal group (D group); · Esketamine nasal spray · Intranasal esketamine · Esketamine intranasal spray · Esketamine intranasal group (K group); Normal saline Physiological saline Intranasal saline Normal saline nasal spray (1 mL) Saline control group (C group)

Eligibility Criteria

Inclusion Criteria

• Children aged 2-12 years ASA physical status I-III Diagnosed with Autism Spectrum Disorder (ASD) by a psychiatrist Scheduled for elective surgery under general anesthesia

Exclusion Criteria

• Cardiac, thoracic/pulmonary, or neurosurgery Congenital disease or severe hepatic/renal dysfunction Allergy to study drugs Neuromuscular disease, cerebral palsy, or epilepsy Other psychiatric or neurologic disorders BMI ≥30 kg/m² Severe upper respiratory tract infection preoperatively Sedatives or analgesics used within 48 hours preoperatively Major life stressor within 1 month pre-op (e.g., family/school change, parental divorce or death) Parent/guardian refuses participation

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Fei

OTHER

Sponsor Role: lead

Responsible Party

Sun Fei

Attending Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Children's Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Countries

China

Central Contacts

Li Zhang, Doctoral degree

Role: CONTACT

drzhangli@njmu.edu.cn

+86 138 1540 6629

Fei Sun, Master's Degree

Role: CONTACT

drsunfei@njmu.edu.cn

+86 181 0061 9994

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

202511028

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

202504034-2

Identifier Type: -

Identifier Source: org_study_id