Remimazolam-Flumazenil Versus Sevoflurane for Hysteroscopic Day Surgery

Ambulatory surgery has become an increasingly important component of modern healthcare systems because it enables rapid recovery, early discharge, efficient utilization of hospital resources, and improved patient satisfaction. The success of ambulatory surgery depends largely on the ability to provide anesthetic care that ensures rapid emergence, minimal postoperative symptoms, and timely discharge without compromising patient safety. Hysteroscopic surgery is one of the most commonly performed ambulatory gynecologic procedures and therefore represents an ideal model for evaluating anesthetic strategies designed to optimize perioperative efficiency and recovery.

Sevoflurane-based balanced anesthesia, typically consisting of intravenous induction followed by maintenance with a volatile anesthetic agent, remains one of the most widely used anesthetic techniques for ambulatory surgery. Although this approach provides reliable hypnosis and favorable surgical conditions, recovery is dependent on anesthetic elimination and individual patient characteristics. Furthermore, volatile anesthetics may contribute to postoperative nausea and vomiting, which remain among the most common causes of delayed discharge and patient dissatisfaction following ambulatory procedures.

Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic that is rapidly metabolized by nonspecific tissue esterases. Compared with conventional anesthetic agents, remimazolam demonstrates predictable pharmacokinetics, limited accumulation, reduced respiratory depression, and favorable hemodynamic stability. Several clinical studies have shown that remimazolam may reduce the incidence and severity of hypotension compared with propofol while providing effective hypnosis for general anesthesia. However, concerns remain regarding delayed awakening and the possibility of residual sedation, particularly in short ambulatory procedures where rapid recovery is essential.

A unique characteristic of remimazolam is the availability of flumazenil, a specific benzodiazepine receptor antagonist capable of rapidly reversing its sedative effects. Planned administration of flumazenil at the end of surgery may allow faster and more predictable emergence than spontaneous recovery alone. Despite this theoretical advantage, evidence supporting a structured remimazolam-flumazenil anesthetic strategy in ambulatory surgery remains limited. Most previous investigations have focused on pharmacodynamic comparisons between remimazolam and propofol, whereas direct comparisons with inhalational balanced anesthesia have been relatively scarce. In addition, few studies have evaluated outcomes that are directly relevant to operating room efficiency and perioperative workflow.

The concept of anesthesia-controlled time has been proposed as a clinically meaningful measure of anesthetic efficiency because it incorporates both induction and emergence phases of anesthesia. Unlike isolated measurements of induction time or awakening time, anesthesia-controlled time reflects the overall contribution of anesthetic management to operating room utilization and turnover. Reductions in anesthesia-controlled time may improve operating room throughput, increase institutional efficiency, and facilitate patient flow in ambulatory surgery centers.

This prospective, single-center, randomized controlled trial is designed to compare remimazolam anesthesia with planned flumazenil reversal and sevoflurane-based balanced anesthesia in adult women undergoing ambulatory hysteroscopic surgery. Eligible participants will be randomly assigned in a 1:1 ratio to receive either remimazolam for induction and maintenance followed by flumazenil reversal at the end of surgery or propofol induction followed by sevoflurane-based balanced anesthesia. Standardized perioperative management protocols will be applied to both groups, including opioid administration, neuromuscular blockade, supraglottic airway management, and electroencephalographic monitoring using the Patient State Index (PSI).

The primary outcome will be anesthesia-controlled time, defined as the sum of induction time and emergence time. Induction time will be measured from initiation of the anesthetic agent to successful placement of the supraglottic airway device, while emergence time will be measured from discontinuation of the primary anesthetic agent to removal of the airway device. This endpoint was selected because it directly reflects operating room efficiency and represents a clinically relevant outcome in ambulatory surgical practice.

Secondary outcomes will evaluate multiple aspects of recovery quality and patient safety. These outcomes include time to achieve an Aldrete score of at least 9, duration of stay in the post-anesthesia care unit, postoperative nausea and vomiting, sore throat, surgical pain, shivering, dizziness, vasopressor requirements, and quality of recovery assessed using the validated Quality of Recovery-15 (QoR-15) questionnaire. The incidence of re-sedation will be evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale together with electroencephalographic monitoring data. Additional recovery variables, including time to eye opening, time to PSI recovery, and time to airway device removal, will also be assessed.

The investigators hypothesize that remimazolam anesthesia with planned flumazenil reversal will reduce anesthesia-controlled time and improve perioperative efficiency while maintaining recovery quality and safety comparable to conventional sevoflurane-based balanced anesthesia. The findings of this study may provide clinically relevant evidence regarding the optimal anesthetic strategy for ambulatory hysteroscopic surgery and may support broader implementation of remimazolam-based anesthesia in short-duration surgical procedures.