Comparison of Recovery From General Anesthesia in Remimazolam With Flumazenil vs. Propofol

Study Overview
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Brief Summary
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This prospective randomized trial aims to compare recovery time from discontinuation of remimazolam followed by flumazenil administration vs. propofol-based total intravenous anesthesia in patients undergoing breast cancer surgery.

Detailed Description
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Adult patients undergoing breast cancer surgery are randomized to receive either remimazolam with flumazenil or propofol-based total intravenous anesthesia. When the surgery is ended, anesthetic agents are discontinued. The study's primary outcome is a comparison of the time to the first eye-opening response to the doctor's command from the discontinuation of anesthetic agents between the groups. Secondary outcomes include the time from anesthetics off to extubation/discharge from operating room (OR), BIS score at eye-opening/extubation/discharge from OR, the incidence of emergence agitation at OR, the PAT score, the modified Aldrete score, modified OAA/S (Observers Assessment of Alertness/Sedation Scale) after PACU administration. In addition, the investigators investigate postoperative pain score at 10/20/30 minutes and postoperative nausea and vomiting after PACU administration, Korean version of quality of recovery-15 in postoperative 24 hours, postoperative pain score and postoperative nausea and vomiting, postoperative opioid consumption in postoperative 24 hours.

Official Title
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Comparison of Recovery From General Anesthesia in Remimazolam With Flumazenil Compared to Propofol-based Total Intravenous Anesthesia in Patients Undergoing Breast Cancer Surgery: a Randomized Controlled Trial

Conditions
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Recovery

Intervention / Treatment
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* Drug: REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO]
* Drug: Flumazenil
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient, age >19, scheduled for breast cancer surgery under general anesthesia Exclusion Criteria: Patients who are not alert before procedure Day surgery BMI ≥35 Hemodynamicaly unstable patients before procedure Patients with history of neromuscular disease or drug use affecting neuromuscular function. Patients with history of adverse reaction of allergic reaction to study drugs Patients who are anticipated to be unable to remove supraglottic airway or endotracheal tube due to severe dyspnea or need for mechanical ventilatory support Use of sedatives (anxiolytics, psychoactive medication, antidepressants, hypnotics) within 24 h Known galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Alcohol or drug dependence Organic brain disorder Patients with hypersensitive to beans or peanut Patients who refuse to participate

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam with flumazenil<br>Patients allocated to remimazolam with flumazenil group receive remimazolam as the main anesthetics during general anesthesia and then flumazenil administration at the end of anesthesia. Remifentanil continuous infusion can be used for hemodynamic stability and analgesia. | Drug: REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO]<br>* Remimazolam Besylate is used as an intervention drug for general anesthesia, followed by flumazenil administration at the end of anesthesia, compared to propofol-based total intravenous anesthesia during breast cancer surgery under general anesthesia<br>* Other names: Remimazolam Besylate;Drug: Flumazenil<br>* Flumazenil is used as an additional intervention drug to facilitate emergence from general anesthesia in the Remimazolam with Flumazenil group.<br>|
| Active Comparator: Propofol-based total intravenous anesthesia<br>Patients allocated to the propofol-based total intravenous anesthesia group receive propofol as the main anesthetics during general anesthesia until the end of anesthesia. Remifentanil continuous infusion can be used for hemodynamic stability and analgesia. | Drug: Propofol<br>* Propofol is used as an active comparator drug for general anesthesia until the end of anesthesia, to be compared to remimazolam besylate during breast cancer surgery under general anesthesia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to eye opening (minute) | The time to the first eye-opening response to the doctor's command from the discontinuation of anesthetic agents | 20 minutes after anesthesia emergence | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to emergence (minutes) | The time from anesthetics off to extubation/discharge from operating room | 20 minutes after anesthesia emergence | 
| Bispectral index score (Score) | A BIS score quantifies changes in the electrophysiologic state of the brain during anesthesia. In patients who are awake, a typical BIS score is 90 to 100. Complete suppression of cortical activity results in a BIS score of 0, known as a flat line. Lower numbers indicate a higher hypnotic effect. | During 20 minutes after anesthesia emergence (3 point : Time from anesthetics off to eye opening/extubation/discharge from operating room) | 
| Incidence of emergence agitation at operating room (n(%)) | Ricker sedation agitated scale ≥5 was defined as emergence agitation, (1-7) | Time Frame: 20 minutes after anesthesia emergence | 
| The modified Aldrete score (Score) | The modified Aldrete score (0-10), Score ≥9 was defined as the possibility of discharge from PACU | 30 minutes after post anaestheisa care unit adminstration | 
| The modified Observers Assessment of Alertness/Sedation Scale (Score) | The modified Observers Assessment of Alertness/Sedation Scale (0-5), Score 5 was defined as respond readily to name spoken in normal tone. | 30 minutes after post anaestheisa care unit adminstration | 
| Postoperative Pain (score) | Numerical rating scales score (0-10) of pain, The higher score was defined as severe pain | 10/20/30 minutes after post anaestheisa care unit administation | 
| Postoperative opioid consumption (The number of analgesic use) | Postoperative opioid requirement | from post anaestheisa care unit administation to post anaestheisa care unit discharge (during 30-40 minutes, upto 1 hours) | 
| Postoperative nausea and vomiting (The incidence of PONV, n(%)) | Postoperative nausea and vomiting | from post anaestheisa care unit administation to post anaestheisa care unit discharge (during 30-40 minutes, upto 1 hours) | 
| Postoperative quality of recovery (score) | Korean version of quality of recovery-15, The higher score was defined as good satisfaction. | upto 24 hours | 
| Postoperative opioid consumption (The number of analgesic use) | Postoperative opioid requirement | upto 24 hours | 
| Postoperative Pain (score) | Numerical rating scales score (0-10) of pain, The higher score was defined as severe pain | upto 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recovery, remimazolam, flumazenil, propofol, safety