Remimazolam Reduces Emergence Delirium in Preschool Children Undergoing Laparoscopic Surgery by Sevoflurane Anesthesia

Remimazolam Reduces Emergence Delirium in Preschool Children Undergoing Laparoscopic Surgery by Sevoflurane Anesthesia: a Double-blinded Randomized Clinical Trial

Emergence delirium (ED) is a manifestation of acute postoperative brain dysfunction that occurs with a relatively high frequency after pediatric anesthesia. The incidence varies depending on the diagnostic criteria used and the combination of administered anesthetic drugs. The use of sevoflurane has been identified as one of the most important risk factors. In the investigators' study，the researchers conducted the current study to investigate whether remimazolam can reduce incidence of ED.

Study Overview

• Status: Recruiting
• Conditions: Emergence Delirium
• Intervention / Treatment: Other: normal saline; Drug: Bolus Remimazolam; Drug: Continuous Infusion Remimazolam

Detailed Description

One hundred twenty children aged 1-6 years old were randomly allocated into three equal groups. Anesthesia is induced with propofol，fentanyl and rocuronium. In group P (Placebo group), anesthesia is maintained by sevoflurane and continuous infusion of normal saline(1ml/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2ml/kg normal saline is administered. In group B (Bolus group), anesthesia is maintained by sevoflurane and continuous infusion of normal saline(1ml/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2mg/kg remimazolam is administered. In group C (continuous infusion group), anesthesia is maintained by sevoflurane and continuous infusion of remimazolam(1mg/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2ml/kg normal saline is administered. Maintain BIS values in the range of 40-60. Recorded the pediatric anesthesia emergence delirium scale (PAED) during the recovery period.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuhang Cai; Phone Number: 18815091585; Email: 838097626@qq.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Recruiting
      • The second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
      • Contact: Yuhang Cai; Phone Number: 18815091585; Email: 838097626@qq.com
      • Contact: Huacheng Liu; Phone Number: 13957770577; Email: huachengliu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. -with American Society of Anesthesiologists (ASA) physical status I or II；
2. -aged 1-6 years；
3. -children with weight for age within the normal range；
4. -were scheduled laparoscopic surgery by sevoflurane anesthesia.

Exclusion Criteria:

1. -children who had Abnormal liver and kidney function,Cardiovascular or endocrine dysfunction;
2. -allergy or hypersensitive reaction to remimazolam;
3. -with any 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: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: group P (Placebo group); Patients were assigned to group P (Placebo group) using a computer-generated random number table	Other: normal saline; Anesthesia is maintained by sevoflurane and continuous infusion of normal saline(1ml/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2ml/kg normal saline is administered; Other Names: Placebo group
Experimental: group B (Bolus group); Patients were assigned to group B (Bolus group) using a computer-generated random number table	Drug: Bolus Remimazolam; Anesthesia is maintained by sevoflurane and continuous infusion of normal saline(1ml/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2mg/kg remimazolam is administered.; Other Names: Bolus group
Experimental: group C (continuous infusion group); Patients were assigned to group C (continuous infusion group) using a computer-generated random number table	Drug: Continuous Infusion Remimazolam; Anesthesia is maintained by sevoflurane and continuous infusion of remimazolam(1mg/kg/h) is administered until about 5min before the end of the surgery. Then intravenous bolus of 0.2ml/kg normal saline is administered.; Other Names: Continuous infusion group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of 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 ≥10 at any time indicates presence of emergence delirium.	Within up to 30 minutes after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End tidal sevoflurane concentration	End tidal sevoflurane concentration at BIS 40-60	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.	Within up to 30 minutes after operation
FLACC scale	The FLACC scale consists of fIve items. Each item is scored 0-2 yielding a total between 0 and 10. The degree of pain increased directly with the total score.	Within up to 30 minutes after operation
Ramsay Sedation Scale score	- The patient is anxious and agitated, restless, or both;; - The patient is cooperative, oriented, and tranquil;; - The patient responds to commands only;; - The patient is asleep and shows a brisk response to a light glabellar tap or loud auditory stimulus;; - The patient is asleep and shows a slow response to a light glabellar tap or loud auditory stimulus;; - The patient is asleep and shows no response to a light glabellar tap or loud auditory stimulus. The degree of sedation increased directly with the total score.	Within up to 30 minutes after operation
Recovery times	The time from discontinuation of sevoflurane to the first open eye of the children and to achieve aldrete≥9	Up to 30 minutes after operation
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% Any adverse effects requiring interventions	Up to 24 hours including intraoperative, and postoperative periods

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: Yuhang Cai, Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2020
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: emergence delirium; remimazolam
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium
• Other Study ID Numbers: SAHoWMU-CR2020-03-113

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