Changes in Autonomic Nervous Activity and Blood Pressure After Anesthesia Induction: Remimazolam Versus Propofol

NCT05635201 | Completed Phase 3

• 1 other identifier: CR-22-138
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to compare the effects of changes in autonomic nervous activity on changes in blood pressure after anesthesia induction between propofol and remimazolam in patients undergoing low-risk surgery. The main questions it aims to answer are:

• Does remimazolam shift sympathovagal balance toward parasympathetic predominance less than propofol?
• Does the less shift in sympathovagal balance toward parasympathetic predominance attenuate the reduction in blood pressure? Participants will be administered either propofol or remimazolam for anesthesia induction, after which the autonomic nervous activity and blood pressure will be measured. Researchers will compare the propofol and remimazolam groups to see if remimazolam causes less shift in sympathovagal balance toward parasympathetic predominance and subsequently attenuates the reduction in blood pressure.

Conditions

General Anesthetics

Outcome Measures

Primary Outcomes (1)

• Difference in low-to-high frequency power ratio (LF/HF) of heart rate variability (HRV) between 5-minute-pre-anesthesia and 5-minute-post-anesthesia induction

  Low-frequency power (LF) and high-frequency power (HF) of heart rate variability (HRV) were calculated with the Fast Fourier Transform applied to a 5-minute-long electrocardiogram (ECG) waveform. LF/HF represents the sympathovagal balance.

  Between 5 minutes before and after anesthesia induction

Secondary Outcomes (48)

• Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes before anesthesia induction

  5 minutes before anesthesia induction

• Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes after anesthesia induction

  5 minutes after anesthesia induction

• Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes after endotracheal intubation

  5 minutes after endotracheal intubation

• Low-frequency power (LF) of heart rate variability (HRV) during 5 minutes before surgical incision

  5 minutes before surgical incision

• High-frequency power (HF) of heart rate variability (HRV) during 5 minutes before anesthesia induction

  5 minutes before anesthesia induction

Other Outcomes (8)

• Deceleration capacity (DC) during 5 minutes before anesthesia induction

  5 minutes before anesthesia induction

• Deceleration capacity (DC) during 5 minutes after anesthesia induction

  5 minutes after anesthesia induction

• Deceleration capacity (DC) during 5 minutes after endotracheal intubation

  5 minutes after endotracheal intubation

Study Arms (2)

Propofol group

ACTIVE COMPARATOR

Receives propofol for anesthesia induction

Drug: Anesthesia induction with propofol

Remimazolam group

EXPERIMENTAL

Receives remimazolam for anesthesia induction

Drug: Anesthesia induction with remimazolam

Interventions

Anesthesia induction with propofol DRUG

After a 10-minute-long acclimation, general anesthesia is induced with 2% propofol at the effect-site concentration of 4 μg/ml based on the Marsh Pharmacokinetic model. The effect-site concentration was maintained at 4 μg/ml until the trachea was intubated. Five minutes after the anesthesia induction, remifentanil was administered at the effect-site concentration of 4 ng/ml based on the Minto pharmacokinetic model until the trachea was intubated. With the initiation of remifentanil infusion, 1 mg/kg of rocuronium was administered following the calibration of the neuromuscular monitoring device. With the train-of-four count of 0, the trachea was intubated. Then, the effect-site concentrations of propofol and remifentanil were decreased to 3 μg/ml and 0 ng/ml, respectively, until the surgical incision was made.

Propofol group

Anesthesia induction with remimazolam DRUG

After a 10-minute-long acclimation, general anesthesia is induced with a 2-minute-long infusion of remimazolam at a rate of 12 mg/kg/hr, after which the infusion rate was reduced to 1 mg/kg/hr and was maintained until the surgical incision was made. Five minutes after the anesthesia induction, remifentanil was administered at the effect-site concentration of 4 ng/ml based on the Minto pharmacokinetic model until the trachea was intubated. With the initiation of remifentanil infusion, 1 mg/kg of rocuronium was administered following the calibration of the neuromuscular monitoring device. With the train-of-four count of 0, the trachea was intubated. Then, the effect-site concentration of remifentanil was decreased to 0 ng/ml until the surgical incision was made.

Remimazolam group

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 20 and 60 years
• American Society of Anesthesiologists physical status of 1
• Elective low-risk surgery requiring general anesthesia, the duration of which is shorter than 2 hours and 30 minutes (e.g., Laparoscopic cholecystectomy, Functional endoscopic sinus surgery, etc.)
• Body mass index less than 30 kg/m2

You may not qualify if:

• Arrhythmias or cardiac conduction disorders
• Disease or medical conditions affecting autonomic nervous activity (hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, cerebrovascular accident, chronic kidney disease, thyroid dysfunction, etc.)
• Valvular heart disease
• Use of medications affecting autonomic nervous activity or cardiac conduction (e.g., beta blocker)
• Limited mouth opening, limited head and upper neck extension, history of obstructive sleep apnea, or Modified Mallampati class 3 or 4
• Serum electrolyte abnormalities
• Severe hypovolemia
• Psychiatric diseases

Sponsors & Collaborators

• Daegu Catholic University Medical Center: lead
• Hana Pharm Co., Ltd.: collaborator

Study Sites (1)

Daegu Catholic University Medical Center

Daegu, 42472, South Korea

Location

MeSH Terms

Interventions

Propofol; remimazolam

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Jonghae Kim, M.D.

  Daegu Catholic University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: December 2, 2022
• Study Start: December 19, 2022
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2023
• Last Updated: October 3, 2023

Record last verified: 2023-10

Locations

KR (1)