Relationship Between Remimazolam and Etomidate in Induction of General Anesthesia

NCT07012902 | Not Yet Recruiting Early Phase 1

• 1 other identifier: yuewei20250519
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

In modern anesthesia practice, anesthesiologists often need to choose a combination of multiple drugs according to the specific conditions and surgical needs of patients, which can not only achieve more fine anesthesia management, but also improve perioperative safety and patient comfort. In clinical practice, anesthesiologists will use etomidate combined with a small dose of remimazolam for anesthesia induction to obtain more stable hemodynamics, prevent intraoperative awareness, and relieve anxiety.However, what is the best dose ratio of etomidate combined with remimazolam, the current literature does not give clear indicators.

Conditions

Induction Anesthesia; Drug Interactions

Keywords

Isoradiation analysis; etomidate; remimazolam

Outcome Measures

Primary Outcomes (5)

• The ED50 value of etomidate in Group A

  The sequential method was used to calculate the median effective dose of etomidate in group A. When the patient's BIS value was between 45 and 60, it was considered a positive response. For the next patient, the dose was reduced by one dose gradient; conversely, if it was a negative response, the dose was increased by one dose gradient. The observation was stopped when the first patient reached the positive-negative turning point, and the next patient with the positive-negative reaction was reached for the seventh turning point. The ED50 of each group was calculated using the probit model.

  one week

• The ED50 value of Remimazolam in Group B

  The sequential method was used to calculate the median effective dose of remimazolam in group B. A positive reaction was defined as a patient's BIS value ranging from 45 to 60. For the next patient, the dose was reduced by one dose gradient if it was a positive reaction, and increased by one dose gradient if it was a negative reaction. The observation was stopped when the next patient with the 7th positive-negative reaction point was reached. The ED50 of each group was calculated using the probit model.

  one week

• Group C D E: etomidate ED50

  The sequential method was adopted to calculate the median effective dose of etomidate for groups C, D, and E separately. A patient was considered to have a positive response if their BIS value was between 45 and 60. For the next patient, the dose was reduced by one dose gradient if it was a positive response, and increased by one dose gradient if it was a negative response. The observation was ended when the next patient with the 7th positive-negative response was reached. The ED50 of each group was calculated using the probit model.

  three weeks

• Isoradiation pattern

  The ED50 determined for groups A and B was plotted on the isoradiogram. The ED50 of etomidate and its 95% confidence interval were plotted on the horizontal axis, and the ED50 of remimazolam and its 95% confidence interval were plotted on the vertical axis. The two ED50 were connected to form an additive line, and the confidence interval was connected to form an additive line with 95% confidence interval. When the two drugs were used together, the effect intensity of the compound drugs fell on the additive line (or within the confidence interval), indicating that the two drugs had additive effect. On the left side of the addition line and confidence interval, it indicated that the two drugs had synergistic effect. If it falls on the right side, it is antagonistic.

  24 hours

• drug correlation coefficient

  The drug correlation coefficient = 1/(actual dose of remimazolam/ED50 of remimazolam + actual dose of etomidate/ED50 of etomidate).

  24 hours

Secondary Outcomes (3)

• muscle tremor

  5 weeks

• Bradycardia

  5 weeks

• hypotension

  5 weeks

Study Arms (5)

Group A (remimazolam induction group)

EXPERIMENTAL

The ED50 of group A was calculated by sequential method

Drug: Etomidate

Group B (etomidate induction group)

EXPERIMENTAL

The ED50 of group B was calculated by sequential method

Drug: Remimazolam

group C (0.25ED50 remimazolam +0.75ED50 etomidate)

EXPERIMENTAL

The ED50 of etomidate in group C were calculated by sequential method.

Drug: Remimazolam-etomidate

Group D (0.5ED50 remimazolam +0.5ED50 etomidate)

EXPERIMENTAL

The ED50 of etomidate in group Dwere calculated by sequential method.

Drug: Remimazolam-etomidate

Group E (0.75ED50 remimazolam +0.25 etomidate)

EXPERIMENTAL

The ED50 of etomidate in group E were calculated by sequential method.

Drug: Remimazolam-etomidate

Interventions

Etomidate DRUG

Group A was induced with etomidate, the initial dose was 0.120mg/kg, and the ratio of adjacent doses was 1:0.6

Group A (remimazolam induction group)

Remimazolam DRUG

Group B was induced with remimazolam, the initial dose was 0.20mg/kg, and the ratio of adjacent doses was 1:0.8

Group B (etomidate induction group)

Remimazolam-etomidate DRUG

In group C, 0.25ED50 remimazolam +0.75ED50 etomidate was used as the initial measurement In group D, 0.5ED50 remimazolam +0.5ED50 etomidate was used as the initial measurement In group E, 0.75ED50 of remimazolam +0.25ED50 of etomidate was used as the initial measurement

Group D (0.5ED50 remimazolam +0.5ED50 etomidate); Group E (0.75ED50 remimazolam +0.25 etomidate); group C (0.25ED50 remimazolam +0.75ED50 etomidate)

Eligibility Criteria

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

You may qualify if:

• Both sexes
• aged 18-60 yr
• ASA physical status I-II
• BIM: 18-28kg/m²

You may not qualify if:

• allergic to remimazolam and etomidate
• in pregnancy or lactation
• serious cardiovascular diseases, long-term alcoholism
• used sedative drugs or opioids within 24 hours
• severe mental illness and myasthenia gravis -

Sponsors & Collaborators

• Second Hospital of Shanxi Medical University: lead

Study Sites (1)

Second Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

MeSH Terms

Interventions

Etomidate; remimazolam

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: June 10, 2025
• Study Start: June 12, 2025
• Primary Completion: June 19, 2025
• Study Completion: July 19, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)