Effects of Flumazenil on Recovery After Total Intravenous Anesthesia With Remimazolam

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

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.

Study Overview

• Status: Recruiting
• Conditions: Elderly Patients; Hip Joint; Flumazenil Adverse Reaction; Remimazolam
• Intervention / Treatment: Drug: normal saline; Drug: Flumazenil

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jaesang BAE, MD; Phone Number: 820553602129; Email: wotkdqo@gmail.com

Study Locations

• Korea, Republic of
  • Gyeongsangnamdo
    • Yangsan, Gyeongsangnamdo, Korea, Republic of, 50612
      • Recruiting
      • Pusan National University Yangsan Hospital
      • Contact: SANGWOOK SHIN, MD, PhD; Phone Number: 82-055-360-2129; Email: shinsw@pusan.ac.kr

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal saline group; Participants are administered 3mL of 0.9% normal saline at the end of anesthesia	Drug: normal saline; 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.; Other Names: Normal saline inj (JW)
Active Comparator: Flumazenil group; Participants are administered 0.3mg(3mL) of flumazenil at the end of anesthesia	Drug: Flumazenil; 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.; Other Names: Flumazenil, Flunil, Bukwang Pharm Co., Ltd

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pusan National University Yangsan Hospital
• Investigators: Study Director: Sangwook Shin, MD. PhD, Pusan National University Yangsan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: July 2, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; GABA Modulators; GABA Agents; Antidotes; Flumazenil
• Other Study ID Numbers: 05-2023-134

Drug and device information, study documents

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