# The 90% effective dose (ED90) of esketamine for inhibiting responses to intraoperative motor stimulation during ambulatory hysteroscopy: a biased-coin up-and-down sequential allocation trial

## TL;DR

This study determines the effective dose of esketamine needed to prevent movement during outpatient hysteroscopy when combined with remimazolam and flurbiprofen axetil.

## Contribution

The study introduces a novel biased-coin design to determine the ED90 of esketamine in an opioid-free anesthetic regimen for ambulatory hysteroscopy.

## Key findings

- The ED90 of esketamine was found to be 0.405 mg/kg (95% CI: 0.370–0.494).
- Anesthesia recovery time averaged 12.1 ± 2.0 minutes with minimal adverse events.
- Mild dizziness occurred in 38% of patients, while other adverse events were rare and resolved spontaneously.

## Abstract

Esketamine and remimazolam co-administration presents a viable opioid-free anesthetic alternative for outpatient hysteroscopy. This study was designed to ascertain the ED90 of esketamine for inhibiting intraoperative movement responses in patients undergoing ambulatory hysteroscopy.

From February 2024 to May 2024, 50 patients undergoing ambulatory hysteroscopy were enrolled. An anesthetic regimen combining esketamine and remimazolam with 50 mg flurbiprofen axetil was employed. The initial esketamine dose was 0.3 mg/kg, with subsequent doses determined using a biased-coin design (9:1). The primary endpoint was the ED90 of esketamine for inhibiting movement responses. Secondary outcomes included anesthesia recovery time, Visual Analog Scale (VAS) scores, and adverse events.

The ED90 of esketamine was 0.405 mg/kg (95% CI: 0.370–0.494). Mean anesthesia recovery time was 12.1 ± 2.0 min. No respiratory depression, hypertension, hypotension, or bradycardia occurred. Mild dizziness was observed in 38% of patients; other adverse events (postoperative nausea and vomiting 4%, coughing 4%, hiccups 4%, transient diplopia 2%) resolved spontaneously. Postoperative VAS scores ranged from 0 to 4 at PACU admission (4% reporting 4), decreasing to 0–1 within four hours.

In ambulatory hysteroscopy under remimazolam-based anesthesia with preemptive analgesia using flurbiprofen axetil, the ED90 of esketamine required to suppress intraoperative body movement was 0.405 mg/kg (95% CI: 0.370–0.494).

The online version contains supplementary material available at 10.1186/s12871-026-03687-1.