Feasibility of Closed-loop TCI Based on New EEG Baseline in the Presence of Low Dose of Esketamine

Feasibility of Closed-loop TCI Based on New BIS Baseline in the Presence of Low Dose of Esketamine: a Randomized Controlled Equivalence Trial.

The propofol-remifentanil closed-loop TCI system based on EEG guidance has been clinically verified, which enables more precise anesthetic dosing. As an adjunct to anesthesia, esketamine has been shown to stabilize hemodynamics, reduce opioid use, and reduce postoperative nausea and vomiting. However, due to its specific electroencephalographic excitatory effect, esketmine's clinical use in close-loop system has been limited. The aim of this experiment was to determine the specific impact of esketamine on EEG and thus obtain a new EEG baseline for close-loop system, which can broaden the application of close-loop TCI system in combination with other drugs.

Study Overview

• Status: Not yet recruiting
• Conditions: Closed-Loop; General Anesthesia With Propofol
• Intervention / Treatment: Drug: Esketamine at low dose; Device: new BIS baseline; Device: original BIS baseline; Drug: an equivalent dose of saline

Detailed Description

The trial is devided into two phases. In the first phase, we statistically analyzed and calculated the changes of BIS by collecting a sample size of EEG changes after administering low dose of esketamine. We used 0.2 mg/kg as a loading dose and followed by a rate of 5ug/kg/min as esketamine administration and observe the changes in BIS each for 30 minutes.

In the second phase, we obtain the BIS quantification value N with the addition of a small dose of esketamine in the first phase and thus obtain a new EEG baseline 50+N. By comparing this EEG-adjusted group with the control group, which run the close-loop system based on original BIS baseline without esketamine, whether the closed-loop system can be better applied based on the new BIS baseline under low dose of esketamine.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: xiaoshan Li, postgraduate; Phone Number: 86 + 17820686302; Email: 1225564331@qq.com
• Study Contact Backup: Name: bo Xu, Doctor, chief director.; Phone Number: 86 + 13802738125; Email: xubo333@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• BMI 18~27kg· m-2;
• American Society of Anesthesiologists (ASA)physical status I~II;
• Undergoing elective laparoscopic surgery.

Exclusion Criteria:

• Known or suspected neurological diseases, tumors, stroke, degenerative neurological diseases, epileptic seizures, serious head injuries, cognitive disorders, post-traumatic stress disorder, mental illnesses, severe depression, psychosis, etc.;
• Contraindications to ketamine, propofol or remifentanil;
• Use of psychotropic drugs within the past 7 days;
• History of drug abuse or drug addiction within the past 30 days or during pregnancy;
• Current participation in any other studies involving other drugs or devices.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjusted-group; After administering esketamine at low dose , this group adjusted drug dosage under closed-loop control based on the new BIS baseline(50＋N).	Drug: Esketamine at low dose; Esketamine at low dose was administered(0.2mg· kg-1, 5 ug· kg-1 continuous infusion) and drug dosage was adjusted(propofol and remifentanil) based on the new BIS baseline ( calculated from the pilot study).; Device: new BIS baseline; Close-loop TCI control was under new BIS baseline(calculated from pilot study) in the presence of esketamine at low dose.
Experimental: Non-adjusted group; After administering esketamine at low dose, this group adjusted drug dosage under closed-loop control based on the original BIS baseline(50).	Drug: Esketamine at low dose; Esketamine at low dose was administered(0.2mg· kg-1, 5 ug· kg-1 continuous infusion) and drug dosage was adjusted(propofol and remifentanil) based on the new BIS baseline ( calculated from the pilot study).; Device: original BIS baseline; Drug dosage was adjused under close-loop control based on original BIS baseline.
Placebo Comparator: control group; This group adjusted drug dosage under closed-loop control based on the original BIS baseline(50) with an equivalent volume of saline.	Device: original BIS baseline; Drug dosage was adjused under close-loop control based on original BIS baseline.; Drug: an equivalent dose of saline; An equivalent dose of saline was given and closed-loop control stared.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BIS, % of time within ± 10 units of the BIS setpoint during closed-loop control	% of time within ± 10 units of the BIS setpoint is the most commonly used metric to evaluate performance of closed-loop control.	time of closed-loop control, started from 10 min after esketamine administration and lasted for 50 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
drug consumption	drug consumption of propofol and remifentanil	time of closed-loop control, started from 10 min after esketamine administration and lasted for 50 min
hemodynamic changes during closed-loop control		time of closed-loop control, started from 10 min after esketamine administration and lasted for 50 min
Postoperative recovery assessment		time to BIS>80, time to regain spontaneous breathing, time to answering questions and time to extubate
occurrance of nausea and vomiting, shivering		From transfer into and out PACU
VAS	visual analgesic score, one of a most commonly used critieria of pain intensity. VAS ranges from 0~10, 0~3 indicates slight or no pain; 4~6 indicates Moderate pain; 7~10 indicates severe pain.	time from PACU administration to transfer out from PACU.
extra analgesic drugs usage		From transfer into and out PACU
intraoperative awareness assessment, 15-item quality of recovery (QoR-15)	Intraoperative awareness is assessed by modified Brice questionnaire; This questionnaire consists of 5 questions. Level of Intraoperative awareness ranges from 0~5. The QoR-15 questionnaire is composed of 15 questions, including physical comfort (5 items), emotional state (4 items), physical independence (2 items), psychological support (2 items), and pain(2 items). The higher of the QoR-15 scores, the better of the quality of recovery after surgery (range is 0 to 150 points).	From postoperative day 1st to day 7th.

Collaborators and Investigators

• Sponsor: bo xu
• Investigators: Study Director: BO xu, doctor, chief director, department of anesthesiology, southern theater general hospital of PLA, Guangzhou, China.

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2025
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: December 7, 2024
• First Submitted That Met QC Criteria: December 7, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: EEG; depth of anesthesia; eskemine; close-loop TCI
• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: GuangzhouGH; 62076253 (Other Grant/Funding Number: Bo Xu); 82472110 (Other Grant/Funding Number: Bo Xu)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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