Determination of ED50 and ED95 With Clinical Efficacy of Intranasal Dexmedetomidine Combined With Esketamine for Preoperative Sedation in Pediatric General Anesthesia

For pediatric patients undergoing general anesthesia, poor anesthesia induction compliance often has adverse effects on individual behavior in the early postoperative period. Dexmedetomidine can reduce the cardiovascular responses and postoperative mental adverse reactions caused by esketamine anesthesia induction [6]. This study aims to explore the ED50 and ED95 and clinical effects of the combination of dexmedetomidine and esketamine nasal drops for preoperative sedation in children of different ages undergoing general anesthesia, providing a theoretical basis for the combined use of dexmedetomidine and esketamine for preoperative sedation in children undergoing general anesthesia.

Study Overview

• Status: Recruiting
• Conditions: Children; Preoperative Anxiety; Dexmedetomidine; Esketamine; Preoperative Sedation; Preoperative Sedation of Children; ED50; ED95
• Intervention / Treatment: Drug: dexmedetomidine; Drug: Esketamine

Detailed Description

Children scheduled for general anesthesia were randomly divided into two groups based on age: Group T consisted of toddlers aged 1 - 3 years old, and Group P consisted of preschool children aged 3 - 6 years old. The initial dose for both groups was dexmedetomidine 1μg/kg and esketamine 0.5mg/kg.

The sedation depth of the children was assessed using the Ramsay Sedation Scale. An unbiased coin - flipping design was adopted: after esketamine 0.5mg/kg was administered intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally. The adjusted dose of dexmedetomidine was 0.25μg/kg. If the sedation of the previous child failed, the intranasal dose of dexmedetomidine for the next child would be increased by 0.25μg/kg. If the sedation of the previous child was successful, a card would be drawn to decide the induction dose for the next patient. A total of 20 cards, which were identical in appearance, were prepared. The probability of administering the same dose was 19/20 (95%), and the probability of reducing the dose for the next patient by 0.25μg/kg was 1/20 (5%).

After drug administration, an anesthesiologist who was unaware of the medication usage would rate the sedation level using the Ramsay Sedation Scale every 5 minutes. The non - invasive blood pressure (NIBP), heart rate (HR), respiratory rate (RR), and blood oxygen saturation (SpO2) were recorded before drug administration (0 minutes, baseline) and at 5, 10, 15, 20, 25, and 30 minutes after drug administration.The onset time was defined as the time from intranasal administration to an RSS score of ≥ 4. Thirty minutes after intranasal administration, an experienced nurse who was unaware of the intranasal drug dose performed intravenous cannulation. The emotional state was assessed using the Emotional State Scale (ESS - 4) during intravenous cannulation. Successful intravenous cannulation was defined as an ESS - 4 score of ≤ 2 during cannulation, regardless of whether the intravenous infusion catheter was successfully inserted.The Pediatric Anesthesia Emergence Delirium (PAED) scale was used to assess the degree of emergence delirium in children. The onset time of sedation (the time to reach an RSS score of ≥4 after intranasal drug administration), surgical time (from the start to the end of the surgery), and awakening time (from the closure of the sevoflurane vaporizer to an Aldrete score of 9 or above) were recorded.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Huacheng Liu; Phone Number: 18957755138; Email: huachengliu@163.com
• Study Contact Backup: Name: Chenrui Zhou; Phone Number: 15157910160; Email: zcr934419@163.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: Huacheng Liu; Phone Number: 18957755138; Email: huachengliu@163.com
      • Contact: Chenrui Zhou; Phone Number: 15157910160; Email: zcr934419@163.com
    • Wenzhou, Zhejiang, China, 325000
      • Not yet recruiting
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: Huacheng Liu; Phone Number: 18957755138; Email: huachengliu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ASA physical status classification Grade I or II;
2. Age 1-6 years old;
3. Children who need to undergo general anesthesia for elective surgery;
4. Weight within the normal range;
5. Signed informed consent form. -

Exclusion Criteria:

1. The child's guardian or the child themselves refuses to participate in the study;
2. Patients with contraindications for sedation/anesthesia or a history of abnormal recovery from sedation/anesthesia;
3. Individuals known to be allergic to the study drugs, opioid drugs, or rescue medications;
4. Individuals with a history of heart, brain, liver, kidney, or metabolic diseases;
5. Individuals with an upper respiratory tract infection within the past two weeks;
6. Individuals with other diseases that may cause harm to the subject. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1-3 years old; The sedation depth of the children was assessed using the Ramsay Sedation Scale. This study was conducted using the biased coin design up - and - down method. The dose for the subsequent participant was determined based on the response of the previous participant. If the previous participant achieved successful sedation, the next participant had a 95% probability of receiving the same dose of dexmedetomidine as the previous participant and a 5% probability of receiving a lower dose of dexmedetomidine (a dose reduction of 0.25 µg/kg). If the previous participant failed to achieve sedation, the dose of dexmedetomidine for the next participant was increased by 0.25 µg/kg until the number of participants reached 40.	Drug: dexmedetomidine; esketamine 0.5mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and the adjusted dose of dexmedetomidine was 0.25μg/kg.; Drug: Esketamine; esketamine 0.5mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and the adjusted dose of dexmedetomidine was 0.25μg/kg.
Experimental: 3-6 years old; The sedation depth of the children was assessed using the Ramsay Sedation Scale. This study was conducted using the biased coin design up - and - down method. The dose for the subsequent participant was determined based on the response of the previous participant. If the previous participant achieved successful sedation, the next participant had a 95% probability of receiving the same dose of dexmedetomidine as the previous participant and a 5% probability of receiving a lower dose of dexmedetomidine (a dose reduction of 0.25 µg/kg). If the previous participant failed to achieve sedation, the dose of dexmedetomidine for the next participant was increased by 0.25 µg/kg until the number of participants reached 40.	Drug: dexmedetomidine; esketamine 0.5mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and the adjusted dose of dexmedetomidine was 0.25μg/kg.; Drug: Esketamine; esketamine 0.5mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and the adjusted dose of dexmedetomidine was 0.25μg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Onset time of sedation	After drug administration, every 5 minutes, an anesthesiologist who was unaware of the medication used assessed the sedation level using the Ramsay Sedation Scale(RSS).Within 30 minutes after the intranasal medication was administered, the Ramsay Sedation Score (RSS) was ≥4.	Within 30 minutes after intranasal administration of dexmedetomidine.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Awakening time	From the closure of the sevoflurane vaporizer to the time when the patient opened their eyes.	Within 1 hour of entering the Post Anesthesia Care Unit (PACU).
Postoperative agitation	The pediatric anesthesia emergence delirium scale consists of five items. Each item is scored 0-4 yielding a total between 0 and 20. The degree of emergence delirium increased directly with the total score. pediatric anesthesia emergence delirium scale ≥12 at any time indicates presence of emergence delirium.	Within up to 15-30 minutes after child's first eye opening in the postoperative period
Number of children with adverse effects	１、Bradycardia and/or hypotension need for hemodynamic support; 2、Desaturation is defined as Oxygen desaturation <90%; 3、Nausea and vomiting; 4、Any adverse effects requiring interventions.	Up to 24 hours including preoperative, intraoperative, and postoperative periods
Intravenous cannulation success rates	Emotional State Score; Calm; Apprehensive, not smiling, tentative behavior, withdrawn; Crying; Thrashing, crying with movements of the arms and legs, resisting	30 minutes after intranasal administration of dexmedetomidine.

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Principal Investigator: Huacheng Liu, Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Children; Dexmedetomidine; Esketamine; Preoperative Anxiety; ED50; ED95; Preoperative sedation; preoperative sedation of children
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Esketamine; Dexmedetomidine
• Other Study ID Numbers: SAHoWMU-CR2025-03-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No