Effect of Remimazolam on Postoperative Nausea and Vomiting

Study Overview
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Brief Summary
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The present trial is to study the effect of low dose remimazolam on postoperative nausea and vomiting (PONV) in patients at risks of PONV (women, postoperative use of opioid, nonsmokers) undergoing laparoscopic cholecystectomy.

Detailed Description
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Postoperative nausea and vomiting (PONV) is a common complication in patients undergoing general anesthesia. It is reported that PONV is observed in 50% of patients 24 hours after general anesthesia and upto 80% in high risk patients. The patients experiencing PONV may experience severe discomfort that it is important to prevent PONV. There are several prophylactic agents for PONV. 5 serotonin receptor antagonist(5-HT3 antagonist) is the most commonly used agent and other agents such as corticosteroid, neurokinin-1 receptor antagonist can also be used. Previous studies have reported the efficacy of benzodiazepine(midazolam) in a low targeting dose as a prophylactic agent of PONV. The efficacy of low dose remimazolam (short acting benzodiazepine) on PONV has not been evaluated. According to Fourth consensus guideline for the management of postoperative nausea and vomiting (2020), three prophylactic anti-emetics are recommended for patients with three or more of the risk factors of PONV. As the patients included in our study have three or more of risk factors of PONV (women, postoperative use of opioid, nonsmokers), three prophylactic anti-emetics are recommended. Our center has routinely been using 5-HT3 receptor antagonist (ramosetron) and corticosteroid (dexamethasone) for women undergoing laparoscopic cholecystectomy. However, we still find many patients complaining nausea and vomiting after operation. Therefore, we are willing to investigate the low supplemental dose of remimazolam on the prophylaxis of PONV.

Official Title
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Effect of Remimazolam on Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Cholecystectomy

Conditions
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Postoperative Nausea and Vomiting

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women undergoing laparoscopic cholecystectomy under general anesthesia. Exclusion Criteria: moderate to severe liver dysfunction (total bilirubin ≧ 3.0 mg/dL / aspartate aminotransferase(AST) or alanine aminotransferase(ALT) ≧ 2.5 times more than normal range) moderate to severe renal dysfunction (serum creatinine ≧ 2.0 mg/dL / end-stage renal disease undergoing hemodialysis) tolerance to benzodiazepines hypersensitivity to anesthetic drugs (Benzodiazepines, Propofol, Remifentanil, Fentanyl citrate, Rocuronium bromide, Flumazenil) acute angle glaucoma alcohol dependence Galactose intolerance, Lactase deficiency, glucose-galactose malabsorption pregnant, breast feeding women BMI >35 kg/m2 uncontrolled diabetes mellitus

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam group<br>Remimazolam is started during induction of anesthesia at the rate of 0.3 mg/kg/hr and stopped 20 minutes before end of operation. | Drug: Remimazolam<br>* Remimazolam is infused at a rate of 0.3 mg/kg/hr from induction of anesthesia until 20 minutes before the end of operation.<br>* Other names: remimazolam group;|
| Placebo Comparator: Control group<br>0.9% normal saline is started during induction of anesthesia at the rate of 0.3 ml/kg/hr and stopped 20 minutes before end of operation. | Drug: Control<br>* Normal saline is infused at a rate of 0.3 ml/kg/hr from induction of anesthesia until 20 minutes before the end of operation.<br>* Other names: control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative nausea and vomit within 24 hours after the end of operation | Nausea is evaluated using 11-point verbal numeric rating scale (VNRS -none:0, mild: 1-3, moderate:4-6, severe 7-10). Vomiting is checked when the patient has vomited or has retching symptom. | Upto 24 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of recovery (QoR-15) 24 hours after the end of the operation | QoR-15 survey is performed 24 hours after the end of the operation. | Upto 24 hours after surgery | 
| pain 24 hours after the end of the operation | pain is evaluated using Numeric rating scale (NRS). | Upto 24 hours after surgery |