Effect of Remimazolam vs Sevoflurane Anesthesia on Incidence of Emergence Agitation and Complications in Children Undergoing Ophthalmic Surgery

Study Overview
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Brief Summary
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As a novel ultra-short-acting benzodiazepines drugs, Remimazolam has been accepted for induction and maintenance of clinical anesthesia. Compared to the traditional benzodiazepines drugs, Remimazolam combines the safety of midazolam with the effectiveness of propofol, and also has the advantages of acting quickly, short half-life, no injection pain, slight respiratory depression, independent of liver and kidney metabolism, long-term infusion without accumulation, and has a specific antagonist: flumazenil. This study aims to investigate whether Remimazolam reduces the incidence of emergence agitation in children after ophthalmic surgery, compared to sevoflurane (RCT).

Official Title
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Effect of Total Intravenous Anesthesia With Remimazolam vs Sevoflurane Inhalation Anesthesia on Incidence of Emergence Agitation and Complications in Children Undergoing Ophthalmic Surgery

Conditions
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Emergence Agitation, Remimazolam, Sevoflurane, Pediatric Ophthalmic Surgery, Anesthesia, General

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Sevoflurane
* Drug: Fentanyl
* Drug: Cisatracurium Besylate
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA Ⅰ-Ⅱ Aged 3-8 years, weight > 10 kg, sex was not limited； Children were scheduled for selective ophthalmic surgery under general anesthesia, Exclusion Criteria: Respiratory infection was present within 4 weeks before surgery. Potential or presence of difficult airways, airway obstruction, sleep apnea, and other contraindications to general anesthesia. The blood routine or blood biochemical indexes were obviously abnormal. Allergy or hypersensitive reaction to test drug, including remimazolam, sevoflurane, and remifentanil. Any child who has taken benzodiazepines in the last 3 months. Unable to cooperate to complete the test, and the guardian refused to attend. Other reasons that researchers hold it is not appropriate to participate in this trial.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a RCTs.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam<br>Induction of anesthesia Slowly inject Remimazolam 0.4-0.8 mg/kg (about 1 minute) until loss of consciousness (LoC), if the degree of sedation is insufficient, additional Remimazolam (0.05 mg/kg each time) is allowed. After the LoC, fentanyl 3-4 ug/kg and cisatracurium besilate 0.1 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope. Maintenance of anesthesia Remimazolam 1 2 mg/kg/h and remifentanil 0.1 0.3 ug/kg/min are injected intravenously to maintain sedation and assistant analgesia, and cisatracurium besilate 0.02 mg/kg is allowed to add as appropriate. During the operation, the dose of anesthetic drugs is adjusted so that the fluctuation of heart rate and blood pressure did not exceed 20 %. | Drug: Remimazolam<br>* Anesthesia was induced with Remimazolam 0.4-0.8 mg/kg (about 1 minute) by intravenous injection until the loss of consciousness (LoC), followed by remimazolam 1-2 mg/kg/h until the end of surgery.<br>Drug: Fentanyl<br>* Anesthesia was induced with fentanyl 3-4 ug/kg by intravenous injection after the LoC.<br>Drug: Cisatracurium Besylate<br>* Anesthesia was induced with cisatracurium besilate 0.1 mg/kg by intravenous injection after the LoC. And the cisatracurium besilate 0.02 mg/kg is allowed to add as appropriate during the operation.<br>Drug: Remifentanil<br>* After the LoC, remifentanil 0.1 0.3 ug/kg/min inject intravenously until the end of surgery.<br>|
| Active Comparator: Sevoflorane<br>Induction of anesthesia After the sevoflurane volatilization tank is adjusted to 8 % and the fresh gas flow rate is 5 L/min, the suitable mask connects with the outlet of the loop and covers the nose of the child. After the LoC, the sevoflurane volatilization tank is set to 3 % and the fresh gas flow rate is 2 L/min to maintain autonomous respiration. At the same time, fentanyl 3-4 ug/kg and cisatracurium besilate 0.1 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope. Maintenance of anesthesia Continuous inhalation of sevoflurane concentration 2 %-3 % and remifentanil 0.1-0.3 ug/kg/min intravenous pump to maintain sedation and assistant analgesia, and cisatracurium besilate 0.02 mg/kg is allowed to add as appropriate. During the operation, the dose of anesthetic drugs is adjusted so that the fluctuation of heart rate and blood pressure did not exceed 20 %. | Drug: Sevoflurane<br>* Anesthesia was induced with 8 % Sevoflorane by sevoflurane volatilization tank until the loss of consciousness (LoC), followed by 2 %-3 % Sevoflorane until the end of surgery.<br>Drug: Fentanyl<br>* Anesthesia was induced with fentanyl 3-4 ug/kg by intravenous injection after the LoC.<br>Drug: Cisatracurium Besylate<br>* Anesthesia was induced with cisatracurium besilate 0.1 mg/kg by intravenous injection after the LoC. And the cisatracurium besilate 0.02 mg/kg is allowed to add as appropriate during the operation.<br>Drug: Remifentanil<br>* After the LoC, remifentanil 0.1 0.3 ug/kg/min inject intravenously until the end of surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of emergence agitation | The PAED 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. PAED scale >12 at any time indicates presence of emergence agitation. | Duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 30 minutes | 
| The incidence of emergence agitation | The Watcha scale consists of four items and scores >2 at any time indicates presence of emergence agitation. | Duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 30 minutes | 
| The incidence of emergence agitation | The 5-point scale consists of five items. The scores ≥4 and lasts for more than 5 minutes indicate presence of emergence agitation. | Duration from the time patients arrived the post-anesthesia care unit to the time of leaving to the ward, average 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic pressure | 30 minutes before induction, immediately after intubation, every 5 minutes after intubation until the child leaves the post-anesthesia care unit and returns to the ward. | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| Diastolic pressure | 30 minutes before induction, immediately after intubation, every 5 minutes after intubation until the child leaves the post-anesthesia care unit and returns to the ward. | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| Mean pressure | 30 minutes before induction, immediately after intubation, every 5 minutes after intubation until the child leaves the post-anesthesia care unit and returns to the ward. | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| Heart rate | 30 minutes before induction, immediately after intubation, every 5 minutes after intubation until the child leaves the post-anesthesia care unit and returns to the ward. | Up to 5 hours including preoperative, intraoperative, and postoperative periods | 
| Recovery times | The period from discontinuation of anesthetic drugs to the recovery of the child's self-consciousness and can respond correctly to external stimuli. | Up to 30 minutes after operation | 
| Delayed emergence | Delayed emergence is defined as failure to shake hands and no significant response to nociceptive stimuli more than 30 minutes after surgery. | Up to 30 minutes after operation | 
| Postoperative Pain | 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. | During the recovery from anesthesia. | 
| Complication | All the perioperative complications are recorded. | During the perioperative period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, General, Pediatric ophthalmic surgery, Emergence Agitation, Remimazolam, Sevoflurane