Esketamine Combined With Remimazolam on Postoperative Sleep Disturbance and Anxiety in Patients

Study Overview
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Brief Summary
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To explore the effects of esketamine combined with remimazolam on postoperative sleep disturbance and anxiety in surgical patients undergoing gastroenteroscopies

Detailed Description
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Postoperative sleep disturbance (PSD) occur in the form of sleep deprivation, circadian rhythm disturbance, and structural abnormalities, and have a high incidence in patients undergoing surgery. Postoperative sleep disorders can lead to postoperative delirium and cognitive dysfunction, aggravate postoperative acute pain, and delay postoperative recovery. Benzodiazepines have a certain sedative hypnotic anti-anxiety effect, and remimazolam as a new benzodiazepine, its sedative hypnotic anti-anxiety effect is worthy of further exploration.Esketamine is an NMDA receptor antagonist with analgesic and sedative effects, and is widely used in clinical treatment of refractory depression. For patients undergoing surgery, in addition to sedation and analgesia, whether the intraoperative use of esketamine has positive effects on postoperative sleep disturbance and anxiety is worth exploring.

Official Title
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Effect of Esketamine Combined With Remimazolam on Postoperative Sleep Disturbance and Anxiety in Patients Undergoing Gastroenteroscopies

Conditions
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Sleep Disturbance

Intervention / Treatment
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* Drug: Esketamine
* Drug: Remimazolam
* Drug: Esketamine and remimazolam
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-65 years old; ASA classification is grade I-III; Elective surgery is proposed BMI of 19-30 kg/m2; Patients who agreed to enroll in this study voluntarily Exclusion Criteria: Those who are known to be allergic to the drug ingredients in this study and their allergic constitution; Allergic history of general anesthesia drugs, opioid drugs, non-steroidal drugs; History of neurological diseases; History of chronic pain; Drug and alcohol addiction; A long history of opioid use; Opiates were given 48 hours before surgery; ASA rating of IV or V; Coronary heart disease, bronchial asthma, severe hypertension, severe blood system dysfunction, liver and kidney function, electrolyte abnormalities; History of gastrointestinal disease (peptic ulcer, Crohn's disease, ulcerative colitis); Respiratory insufficiency, respiratory failure; Patients who refused to use intravenous PCA for analgesia; Pregnant or lactating women; BMI<18 kg/m2 or BMI>30kg/m2; Poor compliance, unable to complete the experiment according to the study plan; Participants who have participated in clinical trials of other drugs within the last 4 weeks; Any circumstances deemed unsuitable for inclusion by the researcher for any reason.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group of patients undergoing gastroenteroscopies with normal saline<br>Patients undergoing gastroenteroscopies were given propofol 2-3mg/kg and 10ml 0.9% saline before the procedure began | Drug: normal saline<br>* Patients undergoing gastroenteroscopies were given propofol 2-3mg/kg and 10ml 0.9% saline before the procedure began<br>* Other names: Group of patients undergoing gastroenteroscopies with normal saline;|
| Active Comparator: Group of patients undergoing gastroenteroscopies with esketamine<br>Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and esketamine 0.2mg/kg before the procedure began | Drug: Esketamine<br>* Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and esketamine 0.2mg/kg before the procedure began<br>* Other names: Group of patients undergoing gastroenteroscopies with esketamine;|
| Active Comparator: Group of patients undergoing gastroenteroscopies with remimazolam<br>Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and remimazolam 0.15mg/kg before the procedure began | Drug: Remimazolam<br>* Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and remimazolam 0.15mg/kg before the procedure began<br>* Other names: Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and remimazolam 0.15mg/kg before the procedure began;|
| Active Comparator: Group of patients undergoing gastroenteroscopies with remimazolam and esketamine<br>Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg， esketamine 0.2mg/kg and remimazolam 0.15mg/kg before the procedure began | Drug: Esketamine and remimazolam<br>* Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg and remimazolam 0.15mg/kg before the procedure began<br>* Other names: Patients undergoing gastroenteroscopies were given propofol 2 to 3mg/kg， esketamine 0.2mg/kg and remimazolam 0.15mg/kg before the procedure began;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep disturbance and anxiety after surgery | Patients completed the sleep quality (AIS, Athens Insomnia Scale) and anxiety (Hospital Anxiety and Depression Scale) rating scales on the day before surgery. HADS consists of 14 items to calculate the patient's comprehensive score, including 7 anxiety related scores and 7 depression related scores. Each question in the questionnaire was scored on a scale of 0-3, so patients scored 0-21 on both anxiety and depression. Scores of 8 points or higher are diagnosed as depression or anxiety.And we asked the patients to fill out these questionnaires on the day 1 and 3 after surgery again to evaluate the changes in sleep quality and anxiety. (The AIS score ranges from 0 to 24 points, and a total score of 6 points or higher indicates a diagnosis of insomnia). . We recorded AIS scores, HDS-A scores and HDS-D scores as separate statistical indicators. | 1 day before surgery, 1 and 3 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score (NRS) | The pain score at rest or after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain. | 1 and 3 days after surgery | 
| Incidence of injection pain | The frequency of injection pain induced by propofol was recorded | Intraoperative | 
| Dosage of drug | The dosage of propofol, esketamine and remimazolam were recorded | Intraoperative | 
| Mean intraoperative blood pressure | The mean intraoperative blood pressure was recorded | Intraoperative | 
| Oxygen saturation | The mean intraoperative oxygen saturation was recorded | Intraoperative | 
| Somatokinetic reaction | The number of intraoperative body movements was recorded | Intraoperative | 
| Operation time | The duration of the patient's operation was recorded(up to 24 h) | Intraoperative | 
| Duration of anesthesia | The patient's duration of anesthesia was recorded(up to 24 h) | After surgery | 
| Time of awakening | The duration from the end of anesthesia to recovery was recorded(up to 24 h) | After surgery | 
| Time to walking down | Record the time from waking up to walking down(up to 24 h) | After surgery | 
| Adverse event | All kinds of adverse events occurred in patients were recorded | Within 3 days after surgery | 
| Exhaust time | Records from end of anesthesia to patients with postoperative exhaust time for the first time | Within 3 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esketamine, remimazolam, anxiety, gastroenteroscopy