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

Phase 4

Recruiting

• Conditions: Preoperative Anxiety; Preoperative Sedation; Children; Dexmedetomidine; Esketamine; ED95; ED50; Preoperative Sedation of Children
• Interventions: Drug: dexmedetomidine; Drug: Esketamine

• Registration Number: NCT06853431
• Lead Sponsor: Second Affiliated Hospital of Wenzhou Medical University

Brief Summary

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.

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 Parental Separation Anxiety Scale (PSAS) was used to assess separation anxiety 30 minutes after drug administration. The Inhalation Induction Compliance Scale (ICC) was used to evaluate the patient's compliance with anesthesia induction after entering the operating room. 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 Timeline

• Study First Submitted: 2025-02-24
• Study First Submitted QC: 2025-02-27
• Status Verified: 2025-03
• Study Start: 2025-03-01
• Study First Posted: 2025-03-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-10
• Primary Completion: 2025-06-30
• Study Completion: 2025-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
1-3 years old	dexmedetomidine	The sedation depth of the children was assessed using the Ramsay Sedation Scale. An unbiased coin - flipping design was adopted: after administering 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. 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%).
1-3 years old	Esketamine	The sedation depth of the children was assessed using the Ramsay Sedation Scale. An unbiased coin - flipping design was adopted: after administering 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. 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%).
3-6 years old	dexmedetomidine	The sedation depth of the children was assessed using the Ramsay Sedation Scale. An unbiased coin - flipping design was adopted: after administering esketamine 0.5 mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and 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%).
3-6 years old	Esketamine	The sedation depth of the children was assessed using the Ramsay Sedation Scale. An unbiased coin - flipping design was adopted: after administering esketamine 0.5 mg/kg intranasally via a nasal dropper, dexmedetomidine 1μg/kg was given intranasally, and 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%).

Primary Outcome Measures

Name	Time	Method
Onset time of sedation	Within 30 minutes after intranasal administration of dexmedetomidine.	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.

Secondary Outcome Measures

Name	Time	Method
Parent - child separation anxiety score	30 minutes after intranasal administration of dexmedetomidine.	Excellent: The patient is not afraid, cooperative, or in a state of sleep. 1 Good: The patient is slightly afraid/crying, but can remain quiet after being comforted. 2 Fair: The patient has moderate fear and crying, and still cannot remain quiet after being comforted. 3 Poor: The patient is crying and needs to be restrained. 4
Induction Compliance Score	3 minutes after entering the operating room.	The compliance of patients with anesthesia induction is assessed using the Inhalation Induction Compliance Scale (ICC).
Awakening time	Within 1 hour of entering the Post Anesthesia Care Unit (PACU).	From the closure of the sevoflurane vaporizer to the time when the patient opened their eyes.
Postoperative agitation	Within up to 15-30 minutes after child's first eye opening in the postoperative period	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.
Number of children with adverse effects	Up to 24 hours including preoperative, intraoperative, and postoperative periods	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.

Trial Locations

Locations (1)

The second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China