Comparison of Remimazolam and Etomidate As Induction Agents for Electroconvulsive Treatment

The goal of this clinical trial is to find if patients would awaken quickly after electroconvulsive treatment when remimazolam is used compared to etomidate. It will also learn about the efficacy of remimazolam. The main questions it aims to answer are:

Will using remimazolam as an induction agent for ECT provide sufficient therapeutic effects? Additionally, when compared to etomidate, will remimazolam lead to a quicker return of spontaneous respiration and faster eye opening after the seizure?

Participants will:

Remimazolam and etomidate will be used in a random order, each administered once for the induction of anesthesia in ECT.

Blood pressure, heart rate, and other vital signs will be monitored during the treatment, and the duration of the seizure as well as the shock energy used to induce the seizure will be recorded.

Study Overview

• Status: Completed
• Conditions: Schizoaffective Disorder; Bipolar; Schizophenia Disorder; Major Depression Disorders
• Intervention / Treatment: Drug: Remimazolam; Drug: Etomidate

Detailed Description

Patients who underwent ECT under general anesthesia between April 2023 and January 2024 were included. The exclusion criteria were as follows: (1) American Society of Anesthesiologists Physical Status ≥3; (2) age <18 or >70 years; and (3) patients with cognitive impairments, such as dementia or delirium. The study sample comprised 30 patients aged 18-70 years who were scheduled to undergo ECT for major depression, schizophrenia, and schizoaffective disorder. The sample size was calculated using G*Power to compare the recovery times between the two groups. On the basis of an effect size of 0.7 obtained from a previous pilot study and a significance level of 0.05, investigators derived a total sample size of 28. Considering a follow-up loss rate of approximately 10%, investigators designed the study to include a total of 30 participants.

The patients were divided into two groups of 15 each and randomly assigned to ei-ther group E or group R using a computer-generated random number table. To minimize variability in recovery speed and response to medication between individuals, investigators devised a crossover study design in which etomidate and remimazolam were administered alternately, with each drug administered once. Patients in group E received etomidate as the induction agent for the first ECT session, followed by remimazolam for the second ECT session a few days later. Conversely, patients in group R received remimazolam as the induction agent for the first ECT session and etomidate for the second ECT session a few days later. The patients and raters were blinded to the administered anesthetic drugs. Blinding was implemented using opaque sealed envelopes that were sequentially numbered.

ECT was conducted following the international standards approved by our institu-tion, using the SpECTrum 5000 Q device (MECTA Corporation, Lake Oswego, OR, USA).

No premedication was administered, and all patients were required to maintain nil per os for at least 8 h before the procedure. During each ECT session, all patients un-derwent non-invasive blood pressure measurement, electrocardiogram, and peripheral oxygen saturation (SpO2) monitoring, and received preoxygenation through an O2 facial mask before anesthesia.

For neuromuscular blockade, succinylcholine (0.8-1.2 mg/kg IV) was used. The an-esthetic dosages were etomidate at 0.15-0.20 mg/kg IV and remimazolam at 0.12-0.15 mg/kg IV. Following admission and monitoring of the patient, preoxygenation was per-formed until SpO2 reached 100%. Then, the induction agent, either etomidate or remi-mazolam, was administered, immediately followed by 100 mcg of remifentanil. Once the patient stopped responding on being called, a cuff was placed on one arm and inflated until the radial artery pulse was no longer detectable. After isolating one arm, succinyl-choline was administered and sufficient time was allowed for fasciculation to resolve before proceeding. After adequate time for the muscle relaxant to take effect, electrical currents were delivered to the brain through electrodes placed on the scalp. The intensity of the current was determined according to an established psychiatric protocol, and in the absence of a seizure, was increased by 10 J in three successive attempts. If a seizure lasting longer than 30 s was induced, the treatment was considered successful. The duration of the seizure and corresponding shock intensity were recorded for each patient.

Following the seizure, mask ventilation was continued until spontaneous respiration returned. The time from the end of the seizure until the patient's spontaneous tidal volume reached ≥200 mL was measured and defined as the self-respiration recovery time. Additionally, the time from the end of the seizure until the patient opened their eyes spontaneously, either in response to a gentle tap or verbal stimulation, was measured and defined as the eye-opening recovery time.

Apart from the induction agent, there were no differences between the two groups in terms of procedural techniques, anesthetic management during surgery, or cardiovascular support.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheon-an, Korea, Republic of, 31116
    • Dankook University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 18-70 years
• Patients diagnosed with major depression, schizophrenia, and schizoaffective disorder who are scheduled to undergo ECT treatment

Exclusion Criteria:

• American Society of Anesthesiologists Physical Status ≥3
• Age <18 or >70 years
• Patients with cognitive impairments, such as dementia or delirium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group Etomidate & Remimazolam; Patients will receive both etomidate and remimazolam once each to compare their effects while minimizing individual differences in response to the medications. Group E will use etomidate first, followed by remimazolam in the subsequent session.	Drug: Remimazolam; Remimazolam is a recently approved medication used for the induction of general anesthesia and maintenance of sedation. There have been no prior studies using remimazolam for the induction of anesthesia in ECT, and this research aims to investigate the feasibility of using remimazolam as an induction agent for ECT.; Drug: Etomidate; Etomidate is widely used in ECT due to its rapid onset, stable hemodynamic profile, and quick recovery. In this study, remimazolam will be used as the experimental group, while etomidate will serve as the control group.
Other: Group Remimazolam & Etomidate; Patients will receive both etomidate and remimazolam once each to compare their effects while minimizing individual differences in response to the medications. Group R will use remimazolam first, followed by etomidate in the subsequent session.	Drug: Remimazolam; Remimazolam is a recently approved medication used for the induction of general anesthesia and maintenance of sedation. There have been no prior studies using remimazolam for the induction of anesthesia in ECT, and this research aims to investigate the feasibility of using remimazolam as an induction agent for ECT.; Drug: Etomidate; Etomidate is widely used in ECT due to its rapid onset, stable hemodynamic profile, and quick recovery. In this study, remimazolam will be used as the experimental group, while etomidate will serve as the control group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self respiration recovery time	After the induction of anesthesia, a shock is administered to induce a seizure. The time is measured from the end of the seizure until the patient's spontaneous tidal volume exceeds 200 ml.	From enrollment to the end of treatment at one week
eye opening recovery time	After the induction of anesthesia, a shock is administered to induce a seizure. The time is measured from the end of the seizure until the patient's spontaneous eye opening.	From enrollment to the end of treatment at one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heartrate	Heartrate measured using electrocardigram, immediately after induction, immediately after shock, and at awakening state, with measurements taken in bpm(beats per minute)	From enrollment to the end of treatment at one week
seizure duration	The duration of the induced seizure following the administration of the shock, with measurements taken in seconds	From enrollment to the end of treatment at one week
shock energy	The amount of energy delivered by the shock used to induce the seizure with the ECT machine, measured in Joules.	From enrollment to the end of treatment at one week
Mean Blood pressure	Mean Blood pressure measured using non-invasive blood pressure, immediately after induction, immediately after shock, and at awakening state, with measurements taken in mmHg	From enrollment to the end of treatment at one week

Collaborators and Investigators

• Sponsor: Yeongseok Yun

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 27, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Psychotic Disorders; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Etomidate
• Other Study ID Numbers: DKUH 2023-02-005-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data generated during the study will be shared and can only be provided to individuals with academic purposes, excluding any personal information about the patients, upon request to the principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No