Effect of Rematazolam Besylate, Propofol, and Sevoflurane Perioperative Sedation on Incidence of Emergence Agitation and Hemodynamics in Patients Undergoing Laparoscopic Abdominal Surgery

Emergence agitation (EA) is a transient, self-limited, non-fluctuating state of psychomotor excitement, which closely revolves around the emergence of general anesthesia. Uncontrolled EA during the recovery period increases the potential risk of injury to patients and medical staff, resulting in varying degrees of adverse consequences, such as elevated blood pressure, incision rupture, bleeding, cardio-cerebrovascular accidents and so on, leading to a great waste of resources.

Accumulating scientific evidence indicates that the incidence of EA is related to the use of perioperative sedative drugs. As a novel ultra-short-acting benzodiazepines drugs, Remimazolam has been accepted for induction and maintenance of clinical anesthesia. Compared to traditional benzodiazepines drugs, Remimazolam combines the safety of midazolam with the effectiveness of propofol, and also has the advantages of acting quickly, short half-life, no injection pain, slight respiratory depression, independent of liver and kidney metabolism, long-term infusion without accumulation, and has a specific antagonist: flumazenil. This study aims to investigate whether perioperative sedation of Remimazolam besylate, propofol, and sevoflurane have different effects on the incidence of emergence agitation and hemodynamics in patients undergoing laparoscopic abdominal surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Anesthesia, General; Emergence Agitation; Laparoscopic Abdominal Surgery; Remimazolam Besylate; Perioperative Sedation
• Intervention / Treatment: Drug: Remifentanil; Drug: Rematazolam Besylate; Drug: Sufentanil; Drug: Cisatracurium Besylate; Drug: Propofol; Drug: Sevoflurane

• Study Type: Interventional
• Enrollment (Anticipated): 1317
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yang Fang; Phone Number: +8618370985324; Email: ndfangyang@163.com

Study Locations

• China
  • Jiangxi
    • Ganzhou, Jiangxi, China
      • People's Hospital of Ganzhou
      • Contact: Guiming Huang, professor; Phone Number: +8615907977699; Email: liyouchun2007@163.com
    • Ganzhou, Jiangxi, China
      • the First Affiliated Hospital of Gannan Medical College, Gannan Medical College
      • Contact: Maolin Zhong, professor; Phone Number: +8613607978802; Email: zml8802@163.com
    • Jiujiang, Jiangxi, China
      • The First People's Hospital of JiuJiang
      • Contact: Shenghong Zhong, professor; Phone Number: +8613607926616; Email: jjmazui@163.com
    • Nanchang, Jiangxi, China
      • the Second Affiliated Hospital of Nanchang University, Nanchang University
    • Nanchang, Jiangxi, China
      • Tumor Hospital of Jiangxi Province
      • Contact: Huaping Xiao, professor; Phone Number: +8613507082466; Email: 463568985@qq.com
    • Shangrao, Jiangxi, China
      • Shangrao People's Hospital
      • Contact: Guoxiong Lin, professor; Phone Number: +8613707033801; Email: lgxmaz@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1 Aged 18-65 years, sex was not limited;
• 2 BMI 18-30kg/m2;
• 3 Patients were scheduled for elective laparoscopic abdominal surgery under general anesthesia, the operation time 2h~4h;
• 4 ASA Ⅰ-III;

Exclusion Criteria:

• 1 Relative contraindications to general anesthesia: Patients with severe heart and lung disease, severe infection, uncontrolled hypertension, diabetes, and severe diabetic complications;
• 2 Abnormal renal and liver function: AST or ALT≥2.5×ULN, TBIL≥1.5×ULN, Serum creatinine concentration (SCC)≥1.5×ULN;
• 3 People with a history of mental illness or long-term use of psychotropic drugs (dementia, schizophrenia), chronic analgesic drug use, alcoholism, and cognitive impairment;
• 4 Any cardiovascular or cerebrovascular accidents occurred within 3 months, such as myocardial infarction, stroke, transient ischemic attack;
• 5 Female pregnant patients;
• 6 Patients undergoing hepatobiliary surgery;
• 7 Allergy to the experimental drug;
• 8 Unable to cooperate to complete the test, the patient or family member rejected the participant;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam Besylate; Induction of anesthesia Slowly inject Remimazolam Besylate 0.3~0.5 mg/kg (about 1 minute) until loss of consciousness (LoC) and BIS<60, if the degree of sedation is insufficient, additional Remimazolam Besylate (0.05 mg/kg each time) is allowed. After the LoC, sufentanil 0.3~0.5 ug/kg and cisatracurium besilate 0.2-0.3 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope.	Drug: Remifentanil; After the LoC, remifentanil 0.1~0.3 ug/kg/min inject intravenously until the end of surgery.; Drug: Rematazolam Besylate; Anesthesia was induced with Rematazolam Besylate 0.3~0.5 mg/kg (about 1 minute) by intravenous injection until the loss of consciousness (LoC) and BIS<60, followed by remimazolam 1-3 mg/kg/h until the end of surgery.; Drug: Sufentanil; Anesthesia was induced with Sufentanil 0.3~0.5 ug/kg by intravenous injection after the LoC and BIS<60.; Drug: Cisatracurium Besylate; Anesthesia was induced with cisatracurium besilate 0.2-0.3 mg/kg by intravenous injection after the LoC and BIS<60, followed by 0.1 mg/kg/h Cisatracurium Besylate during the operation.
Active Comparator: Propofol; Induction of anesthesia Slowly inject Propofol 2~2.5 mg/kg (about 1 minute) until loss of consciousness (LoC) and BIS<60, if the degree of sedation is insufficient, additional Propofol (0.5 mg/kg each time) is allowed. After the LoC, sufentanil 0.3~0.5 ug/kg and cisatracurium besilate 0.2-0.3 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope.	Drug: Remifentanil; After the LoC, remifentanil 0.1~0.3 ug/kg/min inject intravenously until the end of surgery.; Drug: Sufentanil; Anesthesia was induced with Sufentanil 0.3~0.5 ug/kg by intravenous injection after the LoC and BIS<60.; Drug: Cisatracurium Besylate; Anesthesia was induced with cisatracurium besilate 0.2-0.3 mg/kg by intravenous injection after the LoC and BIS<60, followed by 0.1 mg/kg/h Cisatracurium Besylate during the operation.; Drug: Propofol; Anesthesia was induced with Propofol 2~2.5 mg/kg (about 1 minute) by intravenous injection until the loss of consciousness (LoC) and BIS<60, followed by remimazolam 5~12 mg/kg/h until the end of surgery.
Active Comparator: Sevoflurane; Induction of anesthesia Slowly inject Etomidate 0.03 mg/kg (about 1 minute) until loss of consciousness (LoC) and BIS<60, if the degree of sedation is insufficient, additional etomidate (0.03 mg/kg each time) is allowed. After the LoC, sufentanil 0.3~0.5 ug/kg and cisatracurium besilate 0.2-0.3 mg/kg are injected intravenously. After the muscles are sufficiently relaxed and blood circulation is stable, the tracheal tube is inserted under a glide scope.	Drug: Remifentanil; After the LoC, remifentanil 0.1~0.3 ug/kg/min inject intravenously until the end of surgery.; Drug: Sufentanil; Anesthesia was induced with Sufentanil 0.3~0.5 ug/kg by intravenous injection after the LoC and BIS<60.; Drug: Cisatracurium Besylate; Anesthesia was induced with cisatracurium besilate 0.2-0.3 mg/kg by intravenous injection after the LoC and BIS<60, followed by 0.1 mg/kg/h Cisatracurium Besylate during the operation.; Drug: Sevoflurane; Anesthesia was induced with etomidate 0.03 mg/kg (about 1 minute) by intravenous injection until the loss of consciousness (LoC) and BIS<60, followed by 2 %-3 % Sevoflorane until the end of surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of emergence agitation	The Riker Sedation-Agitation Scale (RSAS) score ≥ 5 points indicates the presence of emergence agitation.	Duration from the time patients awakening to the time of departure from post-anesthesia care unit (PACU), average 1 hour.
The incidence of emergence agitation	The Richmond Agitation-Sedation Scale (RASS) ≥ +1 points indicates the presence of emergence agitation.	Duration from the time patients awakening to the time of departure from PACU, average 1 hour.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic pressure		"30 minutes before intubation", "immediately after intubation", "every 5 minutes after intubation until the patient leaves the post-anesthesia care unit, in about six hours", " mornings and afternoons on the 1st, 3rd and 7th day after operation".
Diastolic pressure		"30 minutes before intubation", "immediately after intubation", "every 5 minutes after intubation until the patient leaves the post-anesthesia care unit, in about six hours", " mornings and afternoons on the 1st, 3rd and 7th day after operation".
Mean pressure		"30 minutes before intubation", "immediately after intubation", "every 5 minutes after intubation until the patient leaves the post-anesthesia care unit, in about six hours", " mornings and afternoons on the 1st, 3rd and 7th day after operation".
Heart rate		"30 minutes before intubation", "immediately after intubation", "every 5 minutes after intubation until the patient leaves the post-anesthesia care unit, in about six hours", " mornings and afternoons on the 1st, 3rd and 7th day after operation".
Recovery times	Recovery times is defined as the period from discontinuation of anesthetic drugs to the recovery of the patient's self-consciousness and can respond correctly to external stimuli.	Duration from the time patients awakening to the time of departure from PACU, average 1 hour.
Delayed emergence	Delayed emergence is defined as failure to shake hands and no significant response to nociceptive stimuli more than 30 minutes after surgery.	Duration from the time patients awakening to the time of departure from PACU, average 1 hour.
The incidence of postoperative delirium	The incidence of postoperative delirium was assessed using CAM Scale.	Record in the mornings on the 1st, 3rd and 7th day after operation.
Postoperative Pain	The Numericrating scale (NRS) is grouped from 0 to 10. The degree of pain increased directly with the score.	Record in the mornings on the 1st, 3rd and 7th day after operation.
Complication	All the perioperative complications are recorded.	During the perioperative period, up to 1 week.
Hospitalization time	The length of hospital stay is recorded.	After the patient is discharged from the hospital, average 1 week.
Hospital expenses	Hospitalization costs include total hospitalization costs and anesthesia costs.	After the patient is discharged from the hospital, average 1 week.
30-day all-cause mortality	30-day all-cause mortality is recorded.	30 days after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Nanchang University
• Collaborators: Yichang Humanwell Pharmaceutical Co., Ltd., China

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2022
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): October 31, 2023

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 19, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 19, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Propofol; Sevoflurane; Anesthesia, General; Emergence Agitation; Remimazolam Besylate; Laparoscopic Abdominal Surgery; Perioperative Sedation
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Dyskinesias; Psychomotor Disorders; Delirium; Psychomotor Agitation; Emergence Delirium; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anesthetics, Inhalation; Neuromuscular Agents; Neuromuscular Blocking Agents; Remifentanil; Propofol; Sevoflurane; Sufentanil; Cisatracurium
• Other Study ID Numbers: 2022-EA-2

Drug and device information, study documents

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