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

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

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.

Study Overview

• Status: Completed
• Conditions: Recovery
• Intervention / Treatment: Drug: REMIMAZOLAM BESYLATE 2.5 Mg in 1 mL INTRAVENOUS INJECTION, POWDER, LYOPHILIZED, for SOLUTION [BYFAVO]; Drug: Flumazenil; Drug: Propofol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Seohee Lee, MD, PhD; Phone Number: 82-2-2072-2469; Email: leesen34@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Department of Anesthesiology and Pain Medicine, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam with flumazenil; 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]; 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; Other Names: Remimazolam Besylate; Drug: Flumazenil; Flumazenil is used as an additional intervention drug to facilitate emergence from general anesthesia in the Remimazolam with Flumazenil group.
Active Comparator: Propofol-based total intravenous anesthesia; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: safety; recovery; propofol; remimazolam; flumazenil
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Protective Agents; Hypnotics and Sedatives; GABA Modulators; GABA Agents; Antidotes; Propofol; Flumazenil
• Other Study ID Numbers: Remimazolam_recovery

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