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.

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.