Application of Remimazolam Combined With Esketamine in Painless Gastroscopy and Colonoscopy in Elderly Patients

The objective of this clinical trial is to assess the feasibility of the remimazolam combined with esketamine OFA (opioid-free anesthesia) protocol for painless gastroscopy and colonoscopy in elderly patients and to determine if it is non-inferior to the traditional OA (opioid-containing anesthesia) protocol. The main questions it aims to answer are:

• Is the remimazolam combined with esketamine protocol feasible for painless gastroscopy and colonoscopy in elderly patients?
• Is the OFA protocol superior to the OA protocol?

Participants will:

• During anesthesia induction, the experimental group will receive remimazolam combined with esketamine for anesthesia, while the control group will receive remimazolam combined with remifentanil.
• Record respiratory and circulatory indicators and adverse reaction times.

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Disease
• Intervention / Treatment: Combination product: remimazolam-esketamine; Combination product: remimazolam-remifentanil

Detailed Description

Elderly patients undergoing painless gastroenteroscopy were randomly divided into remazolam + esketamine group (RE group) and remazolam + remifentanil group (RR group). In RE group, anesthesia induction was as follows: Remazolam 0.2mg/kg, esketamine 0.15mg/kg, lidocaine 0.5mg/kg, changtonine 0.2mg. RR group: Anesthesia induction: remazolam 0.2mg/kg, remifentanil 0.2μg/kg, lidocaine 0.5mg/kg, Changtonine 0.2mg. Remazolam and esketamine/remifentanil were added during the operation according to the depth of sedation and movement of the patient. The outcome measures included success rate of sedation, incidence of respiratory depression, incidence of hypotension and bradycardia, postoperative recovery time, incidence of adverse reactions, postoperative satisfaction of patients and gastroenteroscopists.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: LIU Shujie LIU; Phone Number: +86 138 4508 0390; Email: shujieliu312@163.com
• Study Contact Backup: Name: SHI Xiaoqian SHI; Phone Number: +86 188 3424 7923; Email: shixiaoqian005@163.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • The First Affiliated Hospital of Harbin Medical University
      • Contact: LIU Shujie LIU; Phone Number: +86 138 4508 0390; Email: shujieliu312@163.com
      • Contact: SHI Xiaoqian SHI; Phone Number: +86 188 3424 7923; Email: shixiaoqian005@163.com
      • Principal Investigator: SHI Xiaoqian SHI

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients undergoing painless gastroenteroscopy in outpatient clinics;
2. aged 65 years and above;
3. American Society of Anesthesiologists (ASA) grades I - III.

Exclusion Criteria:

1. Patients with abnormal liver or kidney function;
2. known respiratory or endocrine diseases;
3. Patients with uncontrolled hypertension and NYHA classification Ⅲ-Ⅳ;
4. Taking monoamine oxidase inhibitors, sedatives, analgesics, hypnotics, antipsychotics, antiemetics or antidepressants;
5. Addiction to tobacco and alcohol;
6. Patients allergic to the investigational drug;
7. expected difficult airway;
8. Body mass index (BMI) >35kg/m^2;
9. Have participated in other clinical trials within the past three months;
10. Patients with psychosocial illness or cognitive dysfunction and inability to cooperate or communicate.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: remimazolam plus esketamine group; Esketamine combined with remimazolamwas used for anesthesia.	Combination product: remimazolam-esketamine; For elderly patients scheduled for painless gastroenterological endoscopy, remimazolam 0.2mg/kg and esketamine 0.15mg/kg are used for anesthesia induction. During the operation, the dosage is adjusted according to the patient's level of sedation.
Active Comparator: remimazolam plus remifentanil group; Remifentanil combined with remimazolam was used for anesthesia.	Combination product: remimazolam-remifentanil; For elderly patients scheduled for elective painless gastro-intestinal endoscopy, remimazolam 0.2mg/kg and remifentanil 0.2ug/kg are used for anesthesia induction. During the operation, the doses are adjusted according to the depth of sedation of the patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sedation success rate	Successful sedation：① The patient underwent painless gastroenteroscopy;②During anesthesia induction, a single remazolam is not enough to achieve sufficient sedation depth, and it needs to be remedied, and the number of remediations within 15min is less than 5 times; Intraoperative supplementary times ≤5 times within any 15min.③ The patient did not use rescue drugs;Sedation success rate: Number of patients successfully sedated/total number of patients included in the data analysis for this group	From the start of anesthesia induction to the end of the surgery
Incidence of hypotension	Hypotension: systolic blood pressure below 80% of baseline systolic blood pressure or MAP below 80% of baseline MAP; Incidence of hypotension: Number of patients with intraoperative hypotension/total number of patients included in the data analysis for this group	From the start of anesthesia induction to the end of the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
degree of blood oxygen saturation	The blood oxygen saturation was recorded every 2 minutes during the operation. The maximum value is 100. An event where blood oxygen saturation drops below 90 is described as respiratory depression.	From the start of anesthesia induction to the end of the surgery
respiratory rate	The respiratory rate was recorded every 2 minutes during the operation. The normal breathing rate is 12 to 20 breaths per minute.	From the start of anesthesia induction to the end of the surgery
bispectral index	During the surgery, the bilateral frequency index of brain electricity was recorded every 2 minutes. The bispectral index of electroencephalogram is mainly used to assess the depth of sedation, the effect of anesthesia and the state of consciousness. Its value range is from 0 to 100. The higher the value, the higher the degree of consciousness; the lower the value, the deeper the degree of brain inhibition.	From the start of anesthesia induction to the end of the surgery
Heart rate	The heart rate was recorded every 2 minutes during the operation. The normal heart rate is 60 to 100 beats per minute.	From the start of anesthesia induction to the end of the surgery
Blood pressure	The blood pressure was recorded every 2 minutes during the operation.	From the start of anesthesia induction to the end of the surgery
Modified Observer's Assessment of Alertness/Sedation Scale	The MOAA/S, which stands for Modified Observer's Assessment of Alertness/Sedation Scale, assesses the patient's response to sounds or physical stimuli and is scored on a scale of 6 levels: Level 5: Normal alertness, quick response to normal tone of voice; Level 4: Slow response to normal tone of voice; Level 3: Only responds to loud or repeated calls; Level 2: Only responds to slight shaking or tactile stimuli; Level 1: No response to slight shaking or tactile stimuli, but responds to pain stimuli (such as pinching the trapezius muscle); Level 0: No response to pain stimuli. During the surgery, the MOAA/S value was recorded every 2 minutes.	From the start of anesthesia induction to the end of the surgery
Hiccup	Level 0: No hiccups; Level 1: Single mild hiccup; Level 2: Multiple mild hiccups, not affecting the surgical operation (≤ 5 seconds); Level 3: Severe hiccups, affecting the surgical operation (> 5 seconds).	From the start of anesthesia induction to the end of the surgery
cough	Level 0: No choking coughing action; Level 1: A single mild choking coughing action; Level 2: Multiple mild choking coughing actions, which do not affect the surgical operation (≤ 5 seconds); Level 3: Severe coughing (> 5 seconds).	From the start of anesthesia induction to the end of the surgery
Physical movement	Level 1: No activity: Level 2: Slight activity, does not affect operation: Level 3: Obvious activity, has some impact on surgical operation; Level 4: Limb twisting, significantly affects operation.	From the start of anesthesia induction to the end of the surgery
Grade of abdominal wall muscle stiffness	No; moderate (by pressing the abdomen, the abdominal wall muscles become stiff, which affects the colonoscopy examination); Severe (by pressing the abdomen, the abdominal wall muscles become stiff, severely affecting the colonoscopy examination)	From the start of anesthesia induction to the end of the surgery
time index	The induction time of anesthesia is the period from the start of administering remimazolam and remifentanil (esketamine) until the patient loses consciousness and is ready for surgery. The operation time is the duration from the beginning of the gastroscopy procedure to the end of the colonoscopy. The period of full consciousness is from the last administration of anesthetic drugs until the patient regains consciousness. The anesthesia recovery time is the duration from the time the patient regains consciousness to the time when the Aldrete score reaches 9 points.	From the start of anesthesia induction to the end of the surgery
The usage of anesthetic drugs	Record the consumption amounts of lidocaine, esketamine, remifentanil and remimazolam during the operation	From the start of anesthesia induction to the end of the surgery
Adverse event	Adverse events include intraoperative respiratory depression, hypotension, hypertension, bradycardia, tachycardia, arrhythmia, hiccups, choking cough, body movement, abdominal wall rigidity; postoperative nausea, vomiting, headache, dizziness, visual impairment, hallucination, intraoperative awareness, etc.	From the induction of anesthesia to the end of the surgery, and from the end of the surgery to the time when the patient leaves the anesthesia recovery room.
The satisfaction of patients	The patient's satisfaction was measured using the visual analogue scale method. A 10-cm movable ruler with 10 marks was used, with the two ends marked as 0 and 10 respectively. The patient was asked to mark the corresponding position on the ruler that represented their satisfaction level. 0 represented extreme dissatisfaction and 10 represented very satisfaction.	Ask the patient after they regain consciousness.
The satisfaction of doctor	The satisfaction of the doctors was measured using the visual analogue scale method. A 10-cm movable ruler was used, marked with 10 graduations, with the two ends representing 0 points and 10 points respectively. The doctors were asked to mark the corresponding position on the ruler that best represented their satisfaction level. 0 points indicated extreme dissatisfaction, while 10 points indicated very high satisfaction.	At the end of the surgery
Patient pain score	The patient's pain score is classified into four levels: no pain, mild abdominal distension pain (pain is present only when pressed; no pain when not pressed), moderate abdominal pain (pain persists even when not pressed, but is tolerable), and severe abdominal pain (pain is unbearable).	After the patient regained consciousness
Telephone Interview for Cognitive Status	The Telephone Interview for Cognitive Status is a tool used to assess cognitive functions, especially suitable for remote screening of cognitive impairments. TICS is a standardized telephone interview scale that evaluates the cognitive functions of the subjects through questions, including orientation, memory, language ability, calculation ability, etc. It consists of 13 items, with a total score ranging from 0 to 50, and a lower score indicates more severe cognitive impairment.	Before the start of the surgery, after the anesthesia wore off, and on the seventh day after the surgery
The Confusion Assessment Method---CAM	Applicable population: Elderly patients, especially those who have undergone surgery or have cognitive impairments.; Assessment items: It includes 11 indicators, such as acute onset, attention disorder, disordered thinking, disorientation, etc. Each item is scored from 0 to 3 or 0 to 4 points.; Diagnostic criteria: Total score: Below 19 points indicates no delirium, 20 to 22 points indicates suspicion, and above 22 points confirms the diagnosis.	The seventh day after the operation

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Collaborators: First Affiliated Hospital of Harbin Medical University
• Investigators: Study Director: SHI Jinghui SHI

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: May 12, 2025
• First Submitted That Met QC Criteria: May 26, 2025
• First Posted (Actual): June 4, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: esketamine; remimazolam; painless gastroscopy and colonoscopy; success rate of calming down
• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Psychotropic Drugs; Antidepressive Agents; Remifentanil; Esketamine
• Other Study ID Numbers: ChiCTR2500098650

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The original data sharing platform (IPD sharing platform) of ResMan, a clinical trial registration center of China, on June 30, 2028.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; 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