Effects of Flumazenil on Recovery After Total Intravenous Anesthesia With Remimazolam

Study Overview
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Brief Summary
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Remimazolam is a medication that has the advantage of a short half-life and reversibility with flumazenil. In clinical situations, the use of flumazenil for the reversal of sedation is common, but there is no precise indication for its administration. In this study, we aim to investigate the necessity of routine flumazenil use after administering remimazolam for intravenous anesthesia.

Detailed Description
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Remimazolam is a medication that has the advantage of a short half-life and reversibility with flumazenil. Although there are advantages of using flumazenil, such as reduced recovery time and decreased occurrence of postoperative cognitive dysfunction (POCD), it can cause rebound sedation, ventricular arrhythmias, seizures, agitation, and gastrointestinal symptoms. Therefore, routine administration is not recommended. However, in actual clinical situations, it is common to use flumazenil as a routine reversal agent for benzodiazepines, but there is no research on the routine use of flumazenil for reversing the effects of remimazolam in anesthesia or sedation. Factors such as obesity, advanced age, and low plasma albumin concentration can prolong the time for extubation during anesthesia with remimazolam. Therefore, when considering the routine use of flumazenil in waking patients using remimazolam in elderly patients, these factors should be taken into account. However, there is also no specific indication for its accurate administration. Therefore, this study aims to investigate the effects of flumazenil on recovery after total intravenous anesthesia with remimazolam in elderly patients undergoing hip joint surgery

Official Title
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Effects of Flumazenil on Recovery After Total Intravenous Anesthesia With Remimazolam in Elderly Patients Undergoing Hip Joint Surgery: a Prospective Randomized Controlled Study.

Conditions
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Flumazenil Adverse Reaction, Remimazolam, Hip Joint, Elderly Patients

Intervention / Treatment
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* Drug: Flumazenil
* Drug: normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 65 years old scheduled for hip joint surgery Exclusion Criteria: Patients with impaired consciousness or delirium before surgery Patients who are hemodynamically unstable before surgery Patients with a history of neurological or neuromuscular disorders or use of medications that affect neurological or neuromuscular function Patients who have taken sedatives (anti-anxiety medications, antipsychotics, antidepressants, sleep aids) within the past 24 hours Patients with known allergy to benzodiazepine, flumazenil Patients with galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption Patients with hypersensitivity to Dextran40 Patients who have been taking benzodiazepine for long term Patients with end stage renal disease requiring hemodialysis Patients with history of acute angle glaucoma Patients with alcohol or substance dependence ASA classification 4 or 5

Ages Eligible for Study
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Minimum 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal saline group<br>Participants are administered 3mL of 0.9% normal saline at the end of anesthesia | Drug: normal saline<br>* During induction, patients will receive remimazolam 6mg/kg/h with remifentanil TCI 1 4 nanogram/mL. After patient loses consciousness, anesthesia will be maintained with remimazolam 1-2mg/kg/h combined with remifentanil. When procedure ends, infusion remimazolam stops and 0.9% normal saline according to allocated groups.<br>* Other names: Normal saline inj (JW);|
| Active Comparator: Flumazenil group<br>Participants are administered 0.3mg(3mL) of flumazenil at the end of anesthesia | Drug: Flumazenil<br>* During induction, patients will receive remimazolam 6mg/kg/h with remifentanil TCI 1 4 nanogram/mL. After patient loses consciousness, anesthesia will be maintained with remimazolam 1-2mg/kg/h combined with remifentanil. When procedure ends, infusion remimazolam stops and 0.3mg of flumazenil according to allocated groups.<br>* Other names: Flumazenil, Flunil, Bukwang Pharm Co., Ltd;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in eye opening time between the two groups | Time, after stopping injection of remimazolam, to eye opening | Up to two hours | 
| Difference in extubation time between the two groups | Time, after stopping injection of remimazolam, to extubation | Up to two hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual dose of flumazenil | Actual dose of flumazenil | Up to two hours, From end of anesthesia to discharge form the post-anestheic care unit | 
| Occurrence of re-sedation | Richmond Agitation Sedation Scale (RASS) score of -3 or lower(Score range: -5 +4, lower score means more sedated state) | Up to two hours, From end of anesthesia to discharge form the post-anestheic care unit | 
| Side effects of flumazenil usage | Number of Participants with Seizures, agitation, arrhythmias, gastrointestinal symptoms, post operative nausea and vomiting, and degree of pain | Up to two hours, From end of anesthesia to discharge form the post-anestheic care unit |