Clinical Study of Oral Midazolam Combined With Esketamine Administered Intranasally for Pediatric Preoperative Sedation

Children are prone to anxiety and even fear before surgery, and such adverse emotions may not only lead to poor induction of anesthesia, but also increase the incidence of postoperative agitation and even lead to postoperative behavioral changes in children. There are many ways to relieve pediatric anxiety, including preoperative medication, games, and cartoons. Preoperative medication is the most commonly used method to relieve pediatric anxiety.The most commonly used pediatric preoperative sedation drugs are midazolam and esketamine.However, oral midazolam may not produce a sedative effect in 20-40% of patients. A good preoperative anxiety-reducing effect was seen in only 60-80% of cases.Therefore, this trial investigates whether the intranasal combination of esketamine with oral midazolam can produce better results than each of the two drugs alone. This will provide a reference for the selection of safe, reliable and appropriate preoperative sedation methods for pediatric patients and provide evidence-based support for comfort care.

Study Overview

• Status: Recruiting
• Conditions: Anxiety
• Intervention / Treatment: Drug: Midazolam; Drug: Esketamine; Drug: midazolam and esketamine

Detailed Description

A trained member of the research team obtained a baseline The Modified Yale Preoperative Anxiety Scale(mYPAS) after obtaining consent. And corresponding study medication is administered about 30-40 minutes before the anesthesia induction.Vital signs were measured every 5 min after study medication administration.The sedation scores of the children were recorded with University of Michigan Sedation Scale (UMSS) every 10 minutes.The onset time of satisfactory sedation and parental separation anxiety scale was noted.Then recorded the degree of cooperation during inhalation anesthesia induction and recovery times.Moreover, recorded the pediatric anesthesia emergence delirium scale (PAED) during the recovery period.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Huacheng Liu; Phone Number: 18957755138; Email: huachengliu@163.com
• Study Contact Backup: Name: Xulin Zhang; Phone Number: 18583748800; Email: 867237394@qq.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. with American Society of Anesthesiologists (ASA) physical status I or II；
2. aged 2-6 years；
3. children with weight for age within the normal range
4. were scheduled lower abdominal and perineal surgery with an expected operation time shorter than 30 minutes.

Exclusion Criteria:

1. Children who had gastrointestinal,Cardiovascular or endocrine dysfunction;
2. contraindication to preoperative sedation or had a known allergy or hypersensitive reaction to either esketamine or midazolam;
3. with any nasal pathology,organ dysfunction;
4. recently respiratory infection, mental disorder;
5. other reasons that researchers hold it is not appropriate to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: midazolam; Patients were assigned to receive oral midazolam 0.5mg.kg-1 approximately 30-40 minutes before surgery using a computer-generated random number table.	Drug: Midazolam; oral midazolam 0.5mg.kg-1 approximately 30-40 minutes before surgery using a computer-generated random number table.; Other Names: oral midazolam
Experimental: esketamine; Patients were assigned to receive intranasal esketamine 1mg/kg approximately 30-40 minutes before surgery using a computer-generated random number table.	Drug: Esketamine; intranasal esketamine 1mg/kg approximately 30-40 mins before surgery using a computer-generated random number table.; Other Names: Intranasal esketamine
Experimental: midazolam and esketamine; Patients were assigned to receive intranasal esketamine 0.6mg/kg and oral midazolam 0.3mg.kg-1 approximately 30-40 minutes before surgery using a computer-generated random number table.	Drug: midazolam and esketamine; oral midazolam 0.3mg/kg and intranasal esketamine 0.6mg/kg approximately 30-40 mins before surgery using a computer-generated random number table.; Other Names: combination with intranasal esketamine and oral midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The degree of cooperation during inhalation anesthesia induction	Induction Compliance Checklist range from 0 through 10,and lower scores indicate the higher degree of cooperation during inhalation anesthesia induction	During inhalation anesthesia induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery times	The time from discontinuation of sevoflurane to the first open eye of the children and to achieve aldrete≥9	Within up to 30 minutes after child's first eye opening in the postoperative period
Parental separation anxiety scale	A four-point parental separation anxiety scale as follows: -Easy separation,; -Whimpers, but is easily reassured, not clinging,; - Cries and cannot be easily reassured, but not clinging to parents,; - Crying and clinging to parents. The scores of 1 and 2 signified acceptable separation whereas scores of 3 and 4 were classified as difficult separation.	During the preoperative period
Pediatric anesthesia emergence delirium	The pediatric anesthesia emergence delirium scale consists of four 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	Number of children with adverse effects; Bradycardia and/or hypotension need for hemodynamic support; Desaturation is defined as Oxygen desaturation <90%; Salivation; Any adverse effects requiring interventions	Up to 24 hours including preoperative, intraoperative, and postoperative periods
Anxiety before induction of anesthesia	The Modified Yale Preoperative Anxiety Scale: The 22-item measure has five behavioural categories: activity, emotional expressivity, alertness and arousal, vocalizations, and interaction with parents. Total scores range from 23.33 through 100 with higher scores indicating greater anxiety.	Each 10 minutes during the forty minutes of preoperative period
The level of sedation	University of Michigan Sedation Scale: 0 -Awake/Alert 1 -Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds. 2- Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation. 3 - Deeply Sedated: Deep sleep, arousable only with significant physical stimulation. 4 - Unarousable. higher scores mean a higher levels of sedation.	Each 10 minutes during the forty minutes of preoperative period

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2023
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): March 30, 2024

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam; Esketamine
• Other Study ID Numbers: SAHoWMU-CR2023-03-105

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