Effects of Esketamine on Recovery of Consciousness After Propofol Anesthesia

Esketamine is an antagonist of N-methyl-d-aspartate (NMDA) receptor different from other gamma-aminobutyric acid (GABA) receptor agonists. Recent studies showed that subanesthetic doses of ketamine not only deepen anesthesia but also accelerate recovery from isoflurane anesthesia in mice. It is necessary to verify if it applies to human. Besides inducing behavioral unresponsiveness, an optimal and important goal of general anesthesia is to prevent connected consciousness. The results of many studies support the conclusion that anesthesia-related unconsciousness is a consistent functional disconnection of lateral frontoparietal networks.The goal of this clinical trial is to learn if subanaesthetic doses of esketamine works to accelerate the recovery of consciousness from propofol anesthesia. It will also learn about the change of brain network when administrated the esketamine during propofol anesthesia. The main questions it aims to answer are:

1. Does subanaesthetic doses of esketamine can accelerate recovery from propofol anaesthesia?
2. What will happen to brain network connection after different doses of esketamine during propofol anesthesia?

Study Overview

• Status: Recruiting
• Conditions: Post-anesthesia Recovery
• Intervention / Treatment: Drug: Esketamine; Drug: Esketamine; Drug: Saline

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yang Li, Master; Phone Number: +86 18810637134; Email: liyang0519@mail.ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Ruquan Han, Ph.D; Phone Number: 86-13701285393; Email: ruquan.han@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged from 18 years to 50 years
• Patients scheduled for elective operative hysteroscopy
• Willing to sign informed consent

Exclusion Criteria:

• Contraindications of propofol and esketamine
• Contraindications for EEG;
• ASA≥III;
• BMI≥30 kg/m2 or BMI<18 kg/m2;
• The MMSE scale score is lower than the normal value;
• Alcohol or drug abuse;
• Untreated or under-treated hypertension, hyperthyroidism, risk of increased intracranial pressure, audio-visual impairment, history of psychiatric disorders or neurological diseases, malignant tumors or other major diseases;
• Use of other neurological drugs or drugs known to interact with propofol and esketamine in the past 2 weeks;
• Pregnant and lactating women;
• The operation duration is shorter than 15 minutes or longer than 60 minutes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low dose of esketamine; Drug：esketamine (0.3mg/kg)	Drug: Esketamine; Sufentanil(0.1ug/kg) and flurbiprofen axetil(50mg) are administered before induction. Propofol (10 mg/ml) is infused via target-controlled infusions (TCIs). Esketamine hydrochloride (0.3mg/kg total body weight) single intravenous injection after stable plasma concentration of propofol deep sedation.; Drug: Esketamine; Sufentanil(0.1ug/kg) and flurbiprofen axetil(50mg) are administered before induction. Propofol (10 mg/ml) is infused via target-controlled infusions (TCIs). Esketamine hydrochloride (0.6mg/kg total body weight) single intravenous injection after stable plasma concentration of propofol deep sedation.
Experimental: high dose of esketamine; Drug：esketamine(0.6mg/kg)	Drug: Esketamine; Sufentanil(0.1ug/kg) and flurbiprofen axetil(50mg) are administered before induction. Propofol (10 mg/ml) is infused via target-controlled infusions (TCIs). Esketamine hydrochloride (0.3mg/kg total body weight) single intravenous injection after stable plasma concentration of propofol deep sedation.; Drug: Esketamine; Sufentanil(0.1ug/kg) and flurbiprofen axetil(50mg) are administered before induction. Propofol (10 mg/ml) is infused via target-controlled infusions (TCIs). Esketamine hydrochloride (0.6mg/kg total body weight) single intravenous injection after stable plasma concentration of propofol deep sedation.
Experimental: control group; Drug：0.9% saline	Drug: Saline; Sufentanil(0.1ug/kg) and flurbiprofen axetil(50mg) are administered before induction. Propofol (10 mg/ml) is infused via target-controlled infusions (TCIs). The same volume of 0.9% saline instead of esketamine will be given to the control group after stable plasma concentration of propofol deep sedation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery time	Recovery time will be defined as the time from terminating propofol administration to opening eyes to verbal stimuli (participants addressed by name) or, if necessary, mild tactile stimuli (a tap in the shoulder) every 30 seconds.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explicit memory scores and implicit memory scores	The task includes process-dissociation procedure with the word-stem completion. The value ranges from -1 to 1. If the value is less than or equal to 0, it means no memory. If the value is more than 0, it means memory is detected.	2 hours
Subjective experience report	The judges of structured interviews includes three main categories: reports of no recall of any experiences, white reports and reports with specific content.	2 hours
Grooved Pegboard Test points	Time to complete the Grooved Pegboard Test with dominant and non-dominant hand.	2 hours
Original EEG	Four simultaneous channels of frontal EEG waveforms reflect electrical activity of the frontal and pre-frontal cortices of the brain.	2 hours
Patients state index	Processed EEG will be recorded using Sedline (Masimo, Irvine, CA, USA). Patients state index (PSI) uses a proprietary algorithm that incorporates a combination of quantitative EEG parameters and ranges from 0 to 100, with 100 being associated with wakefulness and 0 with an isoelectric EEG.	2 hours
Spectral edge frequency	Spectral edge frequency (SEF) is calculated from the power in frequency ranges. The area under the curve of the power spectrum is calculated and the SEF95 is derived by calculating the frequency at which power is separated into 95 and 5%. SEF90 is calculated in a similar way.	2 hours
Burst suppression ratio	Burst-suppression ratio would be 1.0 for an isoelectric EEG signal and 0 for an EEG signal without any isoelectric periods and represents the percentage of the previous 63 seconds epoch of EEG recognized as those periods longer than 0.5 second, during which the EEG voltage does not exceed approximately +5 to - 5 μV, indicating a severe reduction in the brain's neuronal activity and metabolic rate.	2 hours

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Ruquan Han, PhD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2024
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: esketamine_2024

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No