Effect of Subanesthetic Dose Esketamine on Propofol-refentanil Closed-loop Targeted Controlled Infusion

Chief Physician of the Department of Anesthesiology of the Southern Theater General Hospital

The propofol-refentanil program-controlled closed-loop target-controlled infusion system based on NI guidance has been clinically verified. In the case of clinical use of esketamine, the separation anesthesia properties do not affect the accuracy and safety of closed-loop system guidance. However, whether the specific degree of impact can be quantified, and based on quantitative indicators, this model can be better applied to a wider range of clinical actual conditions and different drug administration backgrounds.

Study Overview

• Status: Not yet recruiting
• Conditions: Esketamine
• Intervention / Treatment: Drug: Subanesthetic dose of esketamine

Detailed Description

The first phase is data collection on the effect of subanesthetic doses of esketamine on NI EEG in closed-loop target-controlled infusion systems for general anesthesia. According to the observation of pre-experiments and the latest literature at home and abroad, foreign studies have confirmed that esketamine does not affect the overall stability of the closed-loop system, and we verified the reliability of this conclusion through pre-experiments. In order to clarify the degree of influence of subanesthetic dose of esketamine on EEG, it is necessary to include a certain amount of esketamine applied to the anesthesia sample of closed-loop target controlled infusion system, through the main observation indicators: the change of EEG NI value after the administration of subanesthetic dose of esketamine during the anesthesia maintenance period, the change of EEG power spectrum, and the quantitative ratio change trend of brain waves (α, β, θ, δ waves). The difference in EEG NI value, power spectrum and dynamic transformation of brain wave increased due to the action of subanesthetic dose of esketamine was obtained, and the difference was quantified by the attribution of data to the degree of change of the actual EEG NI value. According to the preset guidance EEG NI value of the original closed-loop target-controlled infusion drug delivery system 36, the guidance preset value of the closed-loop system of 36+N in the clinical administration scenario of subanesthetic dose of esketamine was reset as the new EEG closed-loop feedback baseline.

The second phase is the validation of the effect of esketamine equivalent to the subanesthetic dose on closed-loop target-controlled infusion general anesthesia based on regulated NI(36+N) feedback.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Bo Xu, professor; Phone Number: +8613802738125; Email: xubo333@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Patients undergoing laparoscopic general anesthesia surgery with anesthesia duration > 60min, 2.18~55 years old, 3.BMI≥18.5kg/m2, 4. ASA Class I~II

Exclusion Criteria:

• Exclude patients with any of the following criteria:

  1. Contraindications to esketamine, propofol or refentanil;
  2. Allergic reactions to egg/soy products; Hypersensitivity to fentanyl analogues;
  3. Known/suspected neurological diseases, tumors, strokes, neurodegenerative diseases, severe head injuries, seizures, previous EEG abnormalities, cognitive deficits, acquired scalp/skull abnormalities, psychiatric diseases, severe depression, post-traumatic stress disorder, psychosis;
  4. Taking psychotropic drugs within the past 7 days,
  5. History of substance abuse/abuse or pregnancy in the past 30 days;
  6. Currently involved in any other research involving drugs or devices.

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: Control group; The preset EEG value of 36 in closed-loop target-controlled infusion is the baseline value of EEG closed-loop feedback guidance (obtained by the team's previous research results)	Drug: Subanesthetic dose of esketamine; Both groups were given NI-guided propofol-refentanil dual-channel closed-loop target-controlled infusion under general anesthesia with a laryngeal mask/endotracheal intubation. The experimental group (EEG feedback index 36+N) and the control group (EEG feedback index 36) were intravenously injected esketamine 0.2mg∙kg-1 before anesthesia induction, followed by continuous 5μg∙kg-1∙min-1 infusion to maintain anesthesia for 30 minutes, and the maximum cumulative dose allowed was 100mg. In both groups, the infusion was stopped 30 minutes before the end of surgery.; Other Names: Esketamine hydrochloride injection
Experimental: Experimental group; Due to the action of esketamine in closed-loop target-controlled infusion, the EEG preset value of 36+N is the baseline value of the new EEG closed-loop feedback guidance (pre-experiment and literature data, N value is 6-8)	Drug: Subanesthetic dose of esketamine; Both groups were given NI-guided propofol-refentanil dual-channel closed-loop target-controlled infusion under general anesthesia with a laryngeal mask/endotracheal intubation. The experimental group (EEG feedback index 36+N) and the control group (EEG feedback index 36) were intravenously injected esketamine 0.2mg∙kg-1 before anesthesia induction, followed by continuous 5μg∙kg-1∙min-1 infusion to maintain anesthesia for 30 minutes, and the maximum cumulative dose allowed was 100mg. In both groups, the infusion was stopped 30 minutes before the end of surgery.; Other Names: Esketamine hydrochloride injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG value	Differences in EEG values between the two groups based on different feedback baselines	From the beginning to the end of the surgery, an average of 4 hours
Anesthesia maintains drug consumption	Two groups of propofol and refentanil consumption	From the beginning to the end of the surgery, an average of 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate	Rate variations and differences throughout the process	From the beginning to the end of the surgery, an average of 4 hours
Blood pressure	Changes and differences in blood pressure throughout the process	From the beginning to the end of the surgery, an average of 4 hours
pulse	Changes and differences in pulse throughout the process	From the beginning to the end of the surgery, an average of 4 hours

Collaborators and Investigators

• Sponsor: bo xu
• Investigators: Principal Investigator: Shengchao Li, Graduate, The First Clinical College of Southern Medical University

Publications and helpful links

General Publications

• Liu N, Chazot T, Hamada S, Landais A, Boichut N, Dussaussoy C, Trillat B, Beydon L, Samain E, Sessler DI, Fischler M. Closed-loop coadministration of propofol and remifentanil guided by bispectral index: a randomized multicenter study. Anesth Analg. 2011 Mar;112(3):546-57. doi: 10.1213/ANE.0b013e318205680b. Epub 2011 Jan 13.
• Napoleone G, van Heusden K, Cooke E, West N, Gorges M, Dumont GA, Ansermino JM, Merchant RN. The Effect of Low-Dose Intraoperative Ketamine on Closed-Loop-Controlled General Anesthesia: A Randomized Controlled Equivalence Trial. Anesth Analg. 2021 Nov 1;133(5):1215-1224. doi: 10.1213/ANE.0000000000005372.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: general anesthesia; Esketamine; NI; closed-loop TCI
• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: Effects of esketamine on EEG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data collection is recorded from anesthesia records in the original medical record and uploaded to Data Digital for sharing and management(https://www.bcg.com/publications/2022/how-to-build-a-data-and-digital-strategy)

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