Anesthesia, General
Conditions
Keywords
Remimazolam, Flumazenil, Emergence delirium, Delirium
Brief 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.
Interventions
DRUGFlumazenil
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.
Sponsors
Korea University Guro Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of 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] | Richmond Agitation & Sedation Scale (RASS) ≥1 is considered emergence delirium. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Severity of POD | From PACU to postoperative day 5 | CAM-severity (CAM-S) is utilized to determine the severity of POD if it occurs. |
| Duration of POD | From PACU to postoperative day 5 | 3D-CAM is utilized to check the duration of POD. |
| Level of consciousness | From emergence to PACU discharge (Immediately after extubation, 15 min after PACU admission, PACU discharge) [within 2 hrs after surgery | Richmond Agitation & Sedation Scale (RASS) is used to evaluate the patients level of consciousness. |
| Incidence of resedation | From emergence to PACU discharge (Immediately after extubation, 15 min after PACU admission, PACU discharge) [within 2 hrs after surgery | Richmond Agitation & Sedation Scale (RASS) ≤-2 is diagnosed as resedation. |
| Time to eye-opening | After remimazolam cessation to eye-opening [within 30 min after remimazolam cessation] | Time taken for patients to open their eyes when their name is gently called after discontinuation of remimazolam. |
| Incidence of postoperative delirium (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] | 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) is used for the evaluation of POD. |
| Preoperative anxiety | 1 day before surgery | Amsterdam Preoperative Anxiety and Information Scale (APAIS) is used to evaluate the patient's anxiety before surgery |
| Postoperative nausea/vomiting (PONV) | From immediately after extubation to PACU discharge [within 2 hours after surgery] | Confirm PONV through patient's symptoms and signs. |
| Postoperative pain | From PACU admission to postoperative day 5 | 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) |
| Postoperative hospital length of stay | From the day of surgery to the day of hospital discharge [within 1 month] | Calculate the days from the date of surgery to the date of hospital discharge. |
| Time to extubation | After remimazolam cessation to extubation [within 30 min after remimazolam cessation] | Time taken for patients to maintain spontaneous breathing and be extubated after remimazolam discontinuation. |
Countries
South Korea
Outcome results
None listed