Low-dose Versus Standard-dose Remimazolam for Prevention of Emergence Agitation After Nasal Surgery

Emergence agitation (EA) is characterized by confusion, agitation, and non-purposeful movements during recovery from general anesthesia. In adult patients undergoing nasal surgery with sevoflurane anesthesia, EA occurs frequently and may result in self-injury, accidental removal of medical devices, postoperative bleeding, prolonged recovery, and increased healthcare burden.

Remimazolam is an ultra-short-acting benzodiazepine that is rapidly metabolized by tissue esterases and can be antagonized with flumazenil. Previous studies have demonstrated that intravenous administration of remimazolam 0.1 mg/kg at the end of surgery reduces the incidence of EA after nasal surgery. However, this dose may produce deeper-than-necessary sedation and increase the occurrence of burst suppression, which has been associated with postoperative delirium.

The present study aims to evaluate whether a lower dose of remimazolam (0.03 mg/kg), corresponding to the supplemental dose commonly used for procedural sedation, can preserve the preventive effect on EA while reducing excessive electroencephalographic suppression and improving recovery characteristics.

This is a prospective, randomized, double-blind, non-inferiority trial conducted at Jeju National University Hospital. Adult patients scheduled for nasal surgery under sevoflurane anesthesia will be randomly assigned in a 1:1 ratio to receive either remimazolam 0.03 mg/kg or remimazolam 0.1 mg/kg immediately after discontinuation of sevoflurane at the end of surgery.

The primary outcome is the incidence of emergence agitation within 15 minutes after extubation, defined as a Riker Sedation-Agitation Scale (SAS) score of 5 or greater. Secondary outcomes include the incidence and duration of burst suppression assessed using the SedLine monitor, Patient State Index (PSi), extubation time, post-anesthesia care unit (PACU) length of stay, and safety outcomes including hypoxemia, hypotension, flumazenil administration, and other adverse events.

• Remimazolam (Drug): Remimazolam will be administered intravenously immediately after discontinuation of sevoflurane at the end of surgery. Participants will receive either 0.03 mg/kg or 0.1 mg/kg according to randomized treatment allocation.

Primary outcomes

• Incidence of emergence agitation [Within 15 minutes after extubation]: The incidence of emergence agitation within 15 minutes after extubation, defined as a Riker Sedation-Agitation Scale (SAS) score of 5 or greater.

Secondary outcomes

• Incidence of burst suppression [From study drug administration until extubation(up to 30 minutes)]: Burst suppression is defined as a suppression ratio greater than 0% lasting for at least 1 minute or occurring repeatedly between study drug administration and extubation.
• Duration of burst suppression [From study drug administration until extubation(up to 30 minutes)]: Cumulative duration of suppression ratio greater than 0% measured using the SedLine monitor.
• Lowest Patient State Index (PSI) [From study drug administration until extubation(up to 30 minutes)]: Lowest Patient State Index recorded after study drug administration.

Sex: All, ages: 18 Years to 79 Years

Inclusion Criteria:

* Adults aged 18 to 79 years.
* Scheduled to undergo elective nasal surgery under sevoflurane-based general anesthesia at Jeju National University Hospital.
* Able to provide written informed consent.

Exclusion Criteria:

* Contraindications to remimazolam.
* History of allergy or hypersensitivity to benzodiazepines.
* Inability to provide informed consent due to cognitive impairment.
* Preexisting psychiatric disorders.
* History of alcohol or substance abuse.
* Inability to assess the Riker Sedation-Agitation Scale (SAS).
* Body mass index (BMI) > 40 kg/m².