The Recovery of Ciprofol, Remimazolam and Remimazolam-Flumazenil for General Anesthesia Undergoing Fundus Surgery: A Single-Center, Prospective, Randomized, Controlled Clinical Study

Abstract

Purpose: Ciprofol (HSK3486 injectable emulsion) is a 2.6-disubstituted phenol derivative that acts similarly to propofol with a fast onset, quick, and stable recovery. Moreover, remimazolam is a new benzodiazepine with a faster onset and recovery than midazolam, and more stable hemodynamics than propofol. We found no relevant literature that directly compared these two drugs. The primary objective of this study was to compare the recovery of HSK3486 with that of remimazolam during successful general anesthesia.

Patients and methods: This prospective, randomized, double-blind study included 93 patients who had undergone fundus surgery. The patients were divided into three groups: HSK3486 (H group), remimazolam-saline (RS group), and remimazolam-flumazenil (RF group). The primary outcome was the time from drug withdrawal to eye opening, and the secondary outcome was the time from drug withdrawal to laryngeal mask removal, the time for Aldrete modified score ≥ 9, intraoperative hemodynamic changes, post-operative adverse events (nausea, vomiting, pain, delirium, re-sedation), and the Quality of Recovery-15 score before surgery and at 1, 7, and 14 days post-operatively.

Results: The RF group showed the shortest eye-opening time: 3.8 (2.8) min vs 13.3 (5.2) min for the H group, P < 0.001; and 11.5 (5.5) min for the RS group, P < 0.001. And laryngeal mask removal time was 5.2 (3.1) min for the RF group vs 14.1 (5.2) min for the H group, P < 0.001; and 12.4 (5.5) min for the RS group, P < 0.001. There were no significant differences in other post-operative outcomes.

Conclusion: The incorporation of flumazenil with remimazolam for total intravenous anesthesia provided rapid and reliable recovery of consciousness, although there were no significant visible differences between HSK3486 and Remimazolam-saline.

Keywords: HSK3486; fungus surgery; recovery; remimazolam; total intravenous anesthesia.

Figure 1

Consolidated standards of reporting trials.(CONSORT) diagram.

Figure 2

The outcomes regarding the emergence. (A) The time to eyes open of Remimazolam-Flumazenil group was shortest among three groups. **P ≤ 0.01. (B) The time to LMA withdrawal of Remimazolam-Flumazenil group was shortest among the three groups. **P ≤ 0.01. (C) Kaplan-Meier survival curve of time to reach Aldrete modified score ≥ 9. (D) Time courses of Mean Bispectral Index change during `surgery. T₁: pre-induction, T₂: loss of consciousness, T₃: after the laryngeal mask airway (LMA) insertion, T₄: operation beginning, T₅: end of surgery, T₅: out of the operating room. Data are shown as mean (standard deviation).

Figure 3

Hemodynamic measurements. T₁: pre-induction, T₂: loss of consciousness, T₃: after the laryngeal mask airway (LMA) insertion, T₄: operation beginning, T₅: end of surgery, T₅: out of the operating room. Data are shown as mean (standard deviation). (A) Time courses of heart rate. Data are shown as mean (standard deviation). (B) Time courses of mean arterial blood pressure. Data are shown as mean (standard deviation).