Impact of Flumazenil on the Emergence Delirium

Anesthesia, General Clinical Trial

Official title:

The Impact of Administration of Flumazenil on the Emergence Delirium in Patients Anesthetized With Remimazolam: a Prospective Randomized Single-blind Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05681377
• Other study ID #: 2022GR0520
• Status: Completed
• Phase: Phase 4
• Start date: March 5, 2023
• Est. completion date: August 11, 2023

Study information

• Verified date: September 2023
• Source: Korea University Guro Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Flumazenil rapidly antagonizes benzodiazepines (BZDs); it may induce agitation, seizure, or delirium, especially when applied to patients who have taken BZDs for a long time. On the contrary, it may help patients regain consciousness in a stable and calm state by appropriately reversing the central nervous system depressant effects of BZDs. In this study, we aim to investigate the impact of flumazenil on the emergence delirium in patients anesthetized with remimazolam, the short-acting BZD drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 11, 2023
• Est. primary completion date: August 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Adult patients aged 19 years or older undergoing surgery under general anesthesia

Exclusion Criteria:

• Peripheral nerve block or Neuraxial block
• Uncontrolled hypertension (HTN) (systolic blood pressure (SBP) =180 mmHg)
• Uncontrolled diabetes mellitus (DM) (HbA1c =9.0%)
• Hepatic dysfunction (Total bilirubin =3.0 mg/mL or Liver enzyme =Upper normal limit x 2.5)
• Renal dysfunction (Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 or Dialysis)
• Moderate or severe chronic obstructive pulmonary disease or Respiratory failure
• Emergency
• Hepatectomy or Liver transplantation
• Intraoperative cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) use
• Head trauma, Increased intracranial pressure, Craniotomy
• Chronic use of benzodiazepines (BZDs)
• Anxiety, Alcohol/Drug dependence, Addiction to tricyclic antidepressants (TCAs)
• Allergic reaction to BZDs, flumazenil, or other drugs used in general anesthesia
• Severe allergy or Anaphylaxis history
• Lactose-related genetic disorders
• Myasthenia gravis or Myasthenia gravis syndrome
• Myocardial infarction or Cerebrovascular events within 6 months
• Symptomatic coronary artery disease
• Organic brain disease
• Cognitive impairment (Inability to understand informed consent)

Related Conditions & MeSH terms

• Anesthesia, General
• Delirium
• Emergence Delirium

Intervention

Drug:
• Flumazenil
After cessation of remimazolam infusion, flumazenil 0.2 mg is administered intravenously over 15 seconds. If consciousness is not adequately restored within 3-5 minutes, a second dose of 0.1 mg intravenously over 15 seconds is administered. If necessary, 0.1 mg may be administered repeatedly at 3-5 minute intervals, and the maximum dose of 1 mg should not be exceeded.

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Korea University Guro Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of emergence delirium	Richmond Agitation & Sedation Scale (RASS) =1 is considered emergence delirium.	From emergence to postanesthesia care unit (PACU) discharge (Immediately after extubation, 15 min after PACU admission, PACU discharge) [within 2 hrs after surgery]
Secondary	Incidence of postoperative delirium (POD)	3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) is used for the evaluation of POD.	From PACU to postoperative day 5(until the discharge date if discharged before 5 days after surgery) [2 times a day in the morning/afternoon]
Secondary	Severity of POD	CAM-severity (CAM-S) is utilized to determine the severity of POD if it occurs.	From PACU to postoperative day 5
Secondary	Duration of POD	3D-CAM is utilized to check the duration of POD.	From PACU to postoperative day 5
Secondary	Level of consciousness	Richmond Agitation & Sedation Scale (RASS) is used to evaluate the patients level of consciousness.	From emergence to PACU discharge (Immediately after extubation, 15 min after PACU admission, PACU discharge) [within 2 hrs after surgery
Secondary	Incidence of resedation	Richmond Agitation & Sedation Scale (RASS) =-2 is diagnosed as resedation.	From emergence to PACU discharge (Immediately after extubation, 15 min after PACU admission, PACU discharge) [within 2 hrs after surgery
Secondary	Time to eye-opening	Time taken for patients to open their eyes when their name is gently called after discontinuation of remimazolam.	After remimazolam cessation to eye-opening [within 30 min after remimazolam cessation]
Secondary	Time to extubation	Time taken for patients to maintain spontaneous breathing and be extubated after remimazolam discontinuation.	After remimazolam cessation to extubation [within 30 min after remimazolam cessation]
Secondary	Preoperative anxiety	Amsterdam Preoperative Anxiety and Information Scale (APAIS) is used to evaluate the patient's anxiety before surgery	1 day before surgery
Secondary	Postoperative nausea/vomiting (PONV)	Confirm PONV through patient's symptoms and signs.	From immediately after extubation to PACU discharge [within 2 hours after surgery]
Secondary	Postoperative pain	Numeric rating scale (NRS) or Visual analogue scale (VAS) is used to determine the patient's pain severity (*NRS and VAS are measured on a 0-10 scale, and the higher the score, the more severe the patient's pain)	From PACU admission to postoperative day 5
Secondary	Postoperative hospital length of stay	Calculate the days from the date of surgery to the date of hospital discharge.	From the day of surgery to the day of hospital discharge [within 1 month]