Anesthesia Induction With Intravenous Bolus or Continuous Infusion of Remimazolam

Comparison of Anesthetic Induction Time and Change of Bispectral Index Between Intravenous Bolus Administration and Continuous Infusion of Remimazolam for Anesthetic Induction: a Prospective Randomized Single-blind Study

Bolus injection and continuous infusion are two widely used methods for intravenous administration of drugs. Bolus injection possibly leads to a rather high drug plasma concentration temporarily, however, it can induce a rapid onset of drug effects and attain a desired clinical state fast. On the contrary, continuous infusion is able to avoid excessive drug levels in plasma, but it takes longer to achieve the proper effect.

In this study, the investigators hypothesize that the bolus injection of remimazolam can reduce anesthesia induction time when compared to the continuous infusion of remimazolam, and also maintain hemodynamic stability. (The researchers will investigate the effect of the bolus injection of remimazolam during anesthesia induction in terms of its safety and efficacy when compared with the continuous infusion.)

Study Overview

• Status: Completed
• Conditions: Anesthesia, General; Adult
• Intervention / Treatment: Drug: Bolus injection of remimazolam; Drug: Infusion of remimazolam

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults 19 years of age or older undergoing surgery under general anesthesia
• ASA I-III

Exclusion Criteria:

• Intraoperative regional blocks (e.g. spinal anesthesia, epidural anesthesia, peripheral nerve block)
• Liver resection or liver transplantation
• Cardiopulmonary bypass
• Uncontrolled HTN (SBP ≧180 mmHg, or ≧160 in patients taking antihypertensive drugs)
• Uncontrolled DM (HbA1c antihypertensive drugs ≧9.0%)
• Total bilirubin ≧3.0 mg/ml or AST or ALS ≧2.5 times the upper limit of normal
• Serum creatinine ≧2.0 mg/ml or ESRD on dialysis
• COPD in need of treatment
• Patients who are expected to have difficulty in tracheal extubation immediately after surgery for postoperative lung management
• Resistance to benzodiazepines
• Hypersensitivity to benzodiazepines, remifentanil, fentanyl citrate, rocuronium, sugammadex, flumazenil, or other anesthetic drugs
• Myasthenia gravis or myasthenic syndrome
• Myocardial infarction, transient ischemic attack, stroke, newly diagnosed coronary artery disease, percutaneous coronary intervention, or coronary artery bypass graft within 6 months
• Implantation of rate-responsive cardiac pacemaker with bioelectrical impedance sensor
• Organic brain disorder, or other neurologic diseases that cannot adequately measure EEG (BIS)
• Severe allergic diseases
• Cognitive impairment that makes it impossible to understand the instructions and informed consent of this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bolus group; Participants in this group are administered remimazolam via the bolus injection method during anesthesia induction.	Drug: Bolus injection of remimazolam; Participants in this group are administered 0.2 mg/kg remimazolam via the bolus injection method for 20 seconds during anesthesia induction. If loss of consciousness (LOC) does not occur, the investigators will administer additional doses of 0.05 mg/kg repeatedly until LOC occurs.; Other Names: Bolus injection of Byfavo
Active Comparator: Infusion group; Participants in this group are administered remimazolam via the continuous infusion method during anesthesia induction.	Drug: Infusion of remimazolam; Participants in this group are administered remimazolam at a rate of 6 mg/kg/hr via the continuous infusion method during anesthesia induction. If loss of consciousness (LOC) does not occur, the investigators will escalate infusion dose to 12 mg/kg/hr until LOC occurs.; Other Names: Continuous infusion of Byfavo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MOAA/SS (sedation level)	The investigators will measure MOAA/SS from the start of remimazolam administration to loss of consciousness (LOC), and compare it between the two groups.	From initiation of remimazolam to LOC (up to 5 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from initiation of drug administration to bispectral index(BIS) <60	The investigators measure how long it takes from the start of remimazolam administration to reach BIS <60.	From initiation of remimazolam to BIS <60 (up to 10 minutes)
BIS	The investigators will measure BIS from the start of remimazolam administration to 15 minutes after surgical incision.	From initiation of remimazolam to 15 minutes after surgical incision
Hemodynamic stability (i.e. blood pressure, heart rate)	The investigators will evaluate hemodynamic stability from the start of remimazolam administration to 15 minutes after surgical incision	From initiation of remimazolam to 15 minutes after surgical incision

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Collaborators: Hana Pharm. Co., Ltd
• Investigators: Principal Investigator: Byung Gun Lim, MD, PhD, Korea University Guro Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Actual): November 25, 2022
• Study Completion (Actual): November 25, 2022

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2022GR0114

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No