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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Emergence Delirium

Intervention / Treatment
-----------------
* Other: normal saline
* Drug: Bolus Remimazolam
* Drug: Continuous Infusion Remimazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -with American Society of Anesthesiologists (ASA) physical status I or II； -aged 1-6 years； -children with weight for age within the normal range； -were scheduled laparoscopic surgery by sevoflurane anesthesia. Exclusion Criteria: -children who had Abnormal liver and kidney function,Cardiovascular or endocrine dysfunction; -allergy or hypersensitive reaction to remimazolam; -with any organ dysfunction; -recently respiratory infection, mental disorder; -other reasons that researchers hold it is not appropriate to participate in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: group P (Placebo group)<br>Patients were assigned to group P (Placebo group) using a computer-generated random number table | Other: normal saline<br>* 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<br>* Other names: Placebo group;|
| Experimental: group B (Bolus group)<br>Patients were assigned to group B (Bolus group) using a computer-generated random number table | Drug: Bolus Remimazolam<br>* 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.<br>* Other names: Bolus group;|
| Experimental: group C (continuous infusion group)<br>Patients were assigned to group C (continuous infusion group) using a computer-generated random number table | Drug: Continuous Infusion Remimazolam<br>* 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.<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
remimazolam, emergence delirium