Comparison of the potency-ratio of ciprofol and propofol on sedative effects in painless hysteroscopy: a randomized double-blind dose-response study

Abstract

Purpose

Ciprofol has been investigated as a potential alternative to propofol for anesthesia because of its tendency to depress the respiratory and circulatory systems to a lesser extent and its association with less pain during injection. However, the relative potency of these two intravenous anesthetics has not been fully determined.

Methods

In this randomized double-blind trial, 232 patients undergoing elective hysteroscopy were allocated to 8 groups (n = 29 each) receiving ciprofol (0.2, 0.3, 0.4, 0.5 mg/kg) or propofol (1.0, 1.5, 2.0, 2.5 mg/kg) as a single intravenous bolus. Dose-response relationships were analyzed using probit regression to estimate ED50(dose giving a 50% response) and ED95(dose giving a 95% response) and nonlinear regression (sigmoidal Emax model) to validate curve fitting. The primary endpoint was the success rates of anesthesia induction (MOAA/S ≤1 within 2 min).

Results

Data from 230 patients were available for analysis. The ED95 of ciprofol [0.53 mg/kg, 95% confidence interval (95% CI) 0.48–0.60] was non-overlapping with propofol (2.16 mg/kg, 95% CI 1.96–2.45), confirming the relative potency ratio for the two drugs 4.1 (95% CI 2.4–9.0). Ciprofol showed significantly lower incidences of injection pain (0% vs. 34.5%, P<0.01) and respiratory depression (27.6% vs. 55.2%, P<0.05) at doses around the ED50.

Conclusion

Ciprofol demonstrated a 4.1:1.0 potency ratio over propofol with superior safety in patients undergoing painless hysteroscopy, supporting its use as an alternative for brief procedures requiring rapid anesthesia induction and recovery.

Trial registration

Clinicaltrials.gov identifier ChiCTR2200059853, May 13, 2022.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12871-025-03416-0.

Introduction

As the predominant choice for brief procedural anesthesia, propofol offers rapid induction and recovery. Nevertheless, its clinical utility is constrained by significant adverse effects including injection-associated pain, respiratory suppression, and hemodynamic compromise [1–4]. These limitations have accelerated the development of novel alternatives such as ciprofol (HSK3486) [5]. Structurally analogous to propofol as a 2,6-disubstituted phenolic compound, ciprofol demonstrates enhanced binding affinity for the gamma-aminobutyric acid type A (GABA_A) receptor [6]. Early-phase clinical investigations (phase Ⅰ-II) indicate ciprofol’s advantageous profile versus propofol, featuring reduced respiratory depression, improved hemodynamic stability, and diminished injection site discomfort during anesthesia induction [6–9]. Phase I-III trials have established 0.4–0.5 mg/kg as its effective sedative dosage range[9–12], ecc ratio relative to propofol based on indirect comparisons or animal models [5, 6, 8, 13, 14].

Despite these developments, a significant knowledge gap remains regarding precise clinical quantification of the ciprofol-propofol potency ratio under standardized clinical conditions. Jin et al. recently applied the up-down sequential allocation method (UDM) to derive a 4.5:1.0 potency estimate during cervical dilation procedures [15]. While this investigation provided valuable preliminary data, UDM’s inherent limitations, such as sequential dose adjustment in small cohorts (n = 60), focus on ED50 rather than ED95, and inability to model full dose-response curves, restrict its utility for comprehensive potency comparisons.

To address these methodological constraints, we designed a randomized, double-blind, dose-response study incorporating several key methodological advancements: (1) pre-defined logarithmic dose intervals (ciprofol: 0.2–0.5 mg/kg; propofol: 1.0–2.5.0.5 mg/kg) to enable comprehensive dose-response characterization; (2) an expanded sample size (n = 232) to enhance statistical power and precision; and (3) specific focus on painless hysteroscopy patients, a clinically important yet understudied population. This approach provides robust, clinically actionable data for optimal anesthetic dosing in this specialized procedure.

Methods

This randomized, double-blinded study received approval from the Ethical Committee of Women’s Hospital, Zhejiang University School of Medicine (Hangzhou, Zhejiang, China) (No.IRB-20220145-R)) and was registered at the Chinese Clinical Trials.gov (No. ChiCTR2200059853). All participants provided written informed consent between June 10,2022 to May 15,2023, with study procedures conducted in the operating rooms of Women’s Hospital, Zhejiang University School of Medicine.

Study patients and design

Eligible participants scheduled for elective hysteroscopy under general anesthesia, meeting the following criteria: (1) American Society of Anesthesiologists (ASA) physical status of Ⅰ-Ⅱ, (2) aged 18–64 years, and (3) BMI 18–25 kg/m². Exclusion criteria: (1) pregnant and nursing women, (2) any contraindication to routine elective hysteroscopy, (3) known allergy to ciprofol or propofol, (4) known severe cardiovascular or pulmonary disease, (5) known psychiatric disorders, (6) participation in other clinical studies, and (7) inability or refusal to give informed consent.

Prior to study initiation, an SPSS 26.0-generated randomization sequence allocated 232 participants equally across eight groups (n = 29 each). An independent research assistant, not involved in patient management or data collection, prepared sequentially numbered, opaque sealed envelopes containing group assignments. This unblinded assistant opened envelopes during recruitment and prepared study drugs accordingly. Participants received intravenous boluses of either ciprofol (Sishuning; Liaoning Hysco Pharmaceutical Co., Ltd.; 50 mg/20 ml): 0.2, 0.3, 0.4, 0.5 mg/kg (Group C₁-C₄), or propofol (Diprivan; Aspen Pharma Trading Limited;200 mg/20 ml): 1.0, 1.5, 2.0, 2.5 mg/kg (Group P₁-P₄). The allocation ratio was 1:1. Ciprofol dosing spanned the established clinical range (0.2–0.5 mg/kg)[11], with logarithmic spacing between concentrations and pragmatic rounding for clinical preparation. Propofol doses (1.0–2.5.0.5 mg/kg) were derived from ciprofol equivalents using an approximately estimated 5:1 potency ratio [6, 8]. Ciprofol (50 mg/20 ml) and propofol (200 mg/20 ml) are white emulsions that are indistinguishable in appearance prepared in identical 50-ml syringes and had a total volume of 40 ml without diluent. To ensure a uniform rate of administration, the patient was given one study drug as a rapid intravenous (IV) bolus using a microinjection pump (SN-50F6 Anesthesia Pump; Sino Medical Ltd, Shenzhen China) for 30 s. An anesthesiologist set the infusion rates according to the following formulae(ml/h): Group C₁, 0.2 (mg/kg) × weight (kg) ÷ 2.5 (mg/ml) × 120 (/h), simplified to weight (kg) × 9.6, similarly, Group C₂, weight (kg) × 14.4, Group C₃, weight (kg) × 19.2, Group C₄ weight (kg) × 24, Group P₁, 1 (mg/kg) × weight (kg) ÷ 10 (mg/ml) × 120 (/h), simplified to weight (kg) × 12, similarly, Group P₂, weight (kg) × 18, Group P₃, weight (kg) × 24, Group P₄, weight (kg) × 30, with doses calculated using actual body weight measured preoperatively. Excluded participants whose actual drug doses administered did not match the intended values. All anesthesia was administered by the same anesthesiologist. The investigator responsible for patient management or data collection was blinded to the group allocation.

Study procedures

Patients abstained from premedication. Standard monitoring commenced upon operating room arrival: noninvasive blood pressure (NIBP) (3-min cycle), electrocardiogram (ECG), pulse oximetry (SpO2) and respiratory rate (RR) (measured by end-tidal carbon dioxide). After 18-gauge IV cannulation in an upper limb vein, supplemental oxygen (5 L/min via Venturi mask) was provided without fluid preload. After 5-min oxygenation and denitrogenation, the patient was given one study drug as a rapid IV bolus using a microinjection pump for 30 s via a three-way stopcock, followed immediately by rapid IV Lactated Ringer’s Solution by fully opening the IV fluid-giving set. The Modified Observer’s Assessment of Alertness/Sedation (MOAA/S)[5, 9, 11, 14, 16, 17] was used to assess the depth of sedation. The MOAA/S and the eyelash reflex were measured every 30 s after administration. The time to loss of the eyelash reflex and side effects were recorded. Baseline measurements of spectral entropy (SE), systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), SpO2 and RR were obtained as the mean of three consecutive readings, which were obtained at 3 min intervals with a difference of less than 10% by monitoring (CARESCAPE Monitor B650, GE Healthcare, Helsinki, Finland) after a short period of rest. The NIBP measured every 1 min after intravenous injection. SE, SBP, MAP, HR, SpO2, and RR were measured at 0.5, 1.5, and 2.5 min from the beginning of the bolus injection, and recorded side effects (pain on injection, respiratory depression, hypotension, and bradycardia). After SBP measurement at 2.5 min, the study was terminated. Anesthesia maintenance then commenced with sufentanil (0.1 ug/kg) and propofol infusion at a rate of 4–12 mg/(kg·h). The surgeon was allowed to start when the SE value was maintained at 50–60 by adjusting the propofol speed.

Endpoints and Definitions

The primary endpoint was the success rates or failure rates of general anesthesia inductions for each dose. Success was defined as a MOAA/S score ≤ 1 (no response to mild prodding or shaking) [10–12, 17] within 2 min after administration of a study drug, and no requirement for intravenous supplementation. Failure was defined as the patient not having a MOAA/S score ≤ 1 within 2 min.

Secondar endpoints included the time to loss of the eyelash reflex and adverse events within 2 min after administration of drugs.

The time to loss of the eyelash reflex was defined as the time from injection of drugs to loss of the eyelash reflex. Adverse events documented pain on injection (patients complained of pain at the injection site during injection or behavioral indicators: facial grimacing, arm withdrawal or tears), hypotension (SBP ≤90 mmHg, > 20% baseline reduction, or MAP < 65 mmHg), respiratory depression (RR < 8 breaths/min, SpO₂ < 95%, or apnea > 60 s) and bradycardia (HR < 50 bpm). Injected atropine or norepinephrine, or received mask ventilation when patients needed.

Probit regression and nonlinear regression was used to analyzed the dose-response data. Estimate of ED₅₀ (dose giving a 50% response) and ED₉₅ (dose giving a 95% response) and the relative potency ratio (95% confidence interval, 95% CI) was performed by probit regression.

Sample size

The sample size was determined based on previous recommendations [18–20] and statistical efficacy analysis[11], In previously published studies, 10 patients were allocated to each dose. Therefore, this study empirically designed a sample size of 29 patients (every group) to achieve narrower confidence limits of dose estimates.

Statistical analysis

Statistical analyses were conducted using SPSS 26.0 (SPSS, Inc., Chicago, IL). Patient characteristics are presented as the mean ± standard deviation (SD) or number of patients N (%) where appropriate, and assessed for randomization homogeneity. Normality distribution was verified via Kolmogorov-Smirnov testing. Between-group comparisons employed Student’s t test for continuous variables between ciprofol and propofol groups, One-way ANOVA or binary logistic regression for multi-dose analyses, Chi-square tests for adverse event incidence (respiratory depression, hypotension, injection pain) across dose groups for each drug.

Dose-response relationships were modeled through probit regression with log10-transformed dose values. For each drug, the numbers of responders at each dose level were tallied. The Pearson goodness-of-fit chi-square statistic was used to test the null hypothesis that the regression model adequately fit the data. Probit regression was used to calculate values for ED50 and ED95 with 95% confidence intervals (95% CIs) and an estimate of relative median potency was determined by comparing the values of ED50. Values of P < 0.05 were considered significant.

Non-linear regression (Sigmoidal Emax model) vs. Probit results for this secondary analysis, values of dose–response data were analyzed with nonlinear regression using GraphPad Prism 9.5(GraphPad Software Inc., USA), as described previously [20]. Response data were entered as x values and were log-transformed. A logistic model was fitted to the drug datasets according to the equation is given in Appendix.

Results

A total of 289 patients were recruitment between June 10, 2022 to September 15. As detailed in Fig. 1, 59 participants were excluded for the following reasons: failed inclusion criteria (n = 30); declined participation (n = 5); surgery cancellation (n = 2); excessive shivering (n = 3); incomplete physiological monitoring data (SE or RR, n = 17); technical failure in signal acquisition (n = 2). The final analytic cohort comprised 230 patients, with baseline demographics presented in Table 1.

Fig. 1.

Consolidated Standards of Reporting Trials flow diagram showing recruitment and flow of patients

Table 1.

Baseline characteristics of patients

Group	C1 N = 29	C2 N = 29	C3 N = 29	C4 N = 29	P1 N = 27	P2 N = 29	P3 N = 29	P4 N = 29
Age, years	35.0 ± 8.1	33.0 ± 5.5	33.9 ± 5.7	34.6 ± 6.0	34.2 ± 6.3	34.7 ± 7.6	35.7 ± 7.5	31.5 ± 5.9
Weight, kg	52.8 ± 6.5	54.5 ± 5.8	55.7 ± 5.7	55.2 ± 4.7	54.0 ± 5.1	54.8 ± 6.5	55.2 ± 4.5	53.2 ± 5.5
Height, cm	159.6 ± 5.5	159.1 ± 4.2	161.4 ± 5.0	161.8 ± 5.7	159.7 ± 4.5	160.0 ± 5.7	160.0 ± 5.5	158.8 ± 5.4
BMI, kg/m 2	20.7 ± 1.7	21.5 ± 1.8	21.3± 1.6	21.1± 1.9	21.2± 1.8	21.4± 2.1	21.6± 1.7	21.2± 2.7
SE	87.8 ± 2.6	88.8 ± 2.4	88.7± 1.6	87.3± 2.6	86.8± 3.9	88.1± 3.2	87.3± 2.5	87.9± 2.7
SBP, mmHg	124.2 ± 12.8	125.3 ± 14.6	121.6 ± 17.3	120.0 ± 12.6	123.0 ± 16.6	123.2 ± 14.8	122.2 ± 14.4	121.4 ± 14.4
MAP, mmHg	93.0 ± 9.6	93.0 ± 9.1	92.1± 12.1	90.0± 8.7	92.7± 11.6	92.0± 10.9	89.6± 10.6	91.2± 10.3
HR, beat/min	75.8 ± 10.1	77.3 ± 14.4	72.6± 11.4	76.4± 13.3	73.7± 13.7	76.9± 14.3	68.7± 8.78	77.8± 10.5
SpO2	99.7 ± 0.6	99.9 ± 0.3	99.9± 0.4	100.0 ± 0.2	99.8± 0.5	99.9± 0.4	99.8± 0.5	99.8± 0.6

values are mean ± SD

Abbreviations: BMI body mass index

The proportions of success for different doses of ciprofol and propofol are shown in Fig. 2. Dose values were logarithmically transformed and success rates were converted to probabilities for analysis. The estimated mean (95% CI) values for ED₅₀ and ED₉₅ of ciprofol were 0.35 (0.33–0.38) mg/kg and 0.53 (0.48–0.60) mg/kg, respectively. The ED₅₀ and ED₉₅ values of propofol were 1.44 (1.32–1.56) mg/kg and 2.16 (1.96–2.45) mg/kg, respectively. The ED95 of ciprofol was non-overlapping with propofol, confirming the relative potency ratio for the two drugs 4.1 (95% CI 2.4–9.0.4.0) (Table 2). The Pearson goodness-of-fit chi-square statistic confirmed that the model adequately fit the data for ciprofol (R² = 0.983, P = 0.943) and propofol (R² = 1.000, P = 0.620) (Fig. 3A), and dose–response curves derived from probit analysis are shown in Fig. 3B. The nonlinear regression (sigmoidal Emax model) to validate curve fitting calculated the ED₅₀ and ED₉₅ of ciprofol and propofol, aligned closely with the probit analysis results. (Table 3; Fig. 4)

Fig. 2.

Success rates of ciprofol (left) and propofol (right) at different doses

Table 2.

Analysis of the success rate performed using probit regression

Drug	ED50, mg/kg	95% CIs	ED95, mg/kg	95% CIs	Median Potency Ratio
Ciprofol	0.35	0.33–0.38	0.53	0.48–0.60	Propofol: Ciprofol 4.1 (2.4- 9.0)
Propofol	1.44	1.32–1.56	2.16	1.96–2.45

results of the success rate performed using probit regression showed, Ciprofol : Probit(p)=4.253+9.407× logdose, Propofol:Probit(p)=-1.498+9.407× log_dose (P=0.620>0.05)

Abbreviations: ED95, dose giving a 95% response, 95% CIs, 95% confidence intervals

Fig. 3.

A Success rates of ciprofol (left) and propofol (right) at different doses. B Dose–response curves for ciprofol (left) and propofol (right) derived from probit analysis. Dashed line indicates the position of the estimate of ED50

Table 3.

Calculated parameters derived by fitting variable slope sigmoidal emax Dose–Response curves to datasets for Ciprofol and Propofol using nonlinear regression

	Ciprofol	95% CIs	Propofol	95% CIs
Log (ED50)	−0.4461	−0.4974-(−0.4002)	0.1656	0.1583–0.1723
ED50, mg/kg	0.3580	0.3182–0.3979	1.464	1.440–1.487
Hill coefficient	6.011	3.364–11.28	8.519	7.351–10.36
R2	0.9904	-	0.9908	-
Log (ED95)	−0.233	-	0.316	0.292–0.338
ED95, mg/kg	0.584	-	2.069	1.957–2.177

Abbreviations: ED50, dose giving a 50% response, ED95, dose giving a 95% response, 95% CIs, 95% confidence intervals

Fig. 4.

Sigmoidal dose–response curves for ciprofol and propofol generated by nonlinear regression

The incidence of pain on injection was significantly lower in the ciprofol group than that in the propofol group (0% vs. 34.5%, P < 0.01) and the incidence of respiratory depression in group C₃ was significantly lower than that in group P₃ (27.6% vs. 55.2%, P<0.05). No difference was found between the groups in terms of the time to loss of eyelash reflex and other adverse effects, such as the incidences of hypotension and bradycardia (Table 4, Supplementary File, Table A). The scatter plots for the major signals (SE, SBP, MAP, HR, and RR) are shown in Supplementary File, Figure B-E.

Table 4.

Other endpoints and adverse events at doses around the ED50

	Group C3	Group P2	P
Dose(mg/kg)	0.4	1.5
Time of loss eyelash reflex, s	58.40 ± 40.06	57.63 ± 22.43	0.942
Respiratory depression, n (%)	8(27.6)	9(31.0)	0.773
Hypotension, n (%)	8(27.6)	9(31.0)	0.773
Bradycardia	0	0	-
injection pain, n (%)	0	10(34.5)	< 0.01
	Group C3	Group P3	P
Dose(mg/kg)	0.4	2.0
Time of loss eyelash reflex, s	58.40 ± 40.06	51.48 ± 29.99	0.521
Respiratory depression, n (%)	8(27.6)	16(55.2)	0.045
Hypotension, n (%)	8(27.6)	9(31.0)	0.773
Bradycardia	0	0	-
Injection Pain, n (%)	0	10(34.5)	< 0.01

values are mean ± SD or number of patients, N (%)

Discussion

This investigation established dose-response relationships for single-bolus ciprofol or propofol through induction success assessment. Key pharmacodynamic findings demonstrated. The estimated mean (95% CI) values for ED₉₅ were 0.53 (0.48–0.60) mg/kg for ciprofol and 2.16 (1.96–2.45) mg/kg for propofol. The estimated relative potency ratio was 4.1 (95% CI, 2.4 to 9.0) for ciprofol and propofol. Ciprofol demonstrated significantly lower incidence of injection pain (0% vs. 34.5%, P < 0.01) and respiratory depression (27.6% vs. 55.2%, P < 0.05) at doses around the ED50 by the eight-dose group design.

While previous studies reported that the recommended doses range of ciprofol for sedation were 0.4–0.5 mg/kg[9–12, 16, 21], and demonstrated noninferiority to 1.5 mg/kg and 2.0 mg/kg of propofol [9, 12, 16]. Nevertheless, these predominantly focused on ED50[15, 22], a parameter ensuring efficacy in merely 50% of patients. Methodologically advancing beyond existing literature, our probit-derived dose-response analysis quantifies ED95 estimates (0.53 mg/kg ciprofol vs. 2.16 mg/kg propofol) directly inform protocols to achieve 95% efficacy, a threshold critical for minimizing intraoperative awareness risk in hysteroscopy.

To date, clinical evidence directly quantifying the ciprofol-propofol relative potency for sedation in clinical circumstances remains limited [5, 6, 8, 9, 12–14, 16]. Ciprofol had 4–5 times higher efficacy than propofol based on animal models [6, 13, 23] or indirect comparisons[5, 8, 14], which was an interval (4:1 to 5:1). Although Jin et al. pioneered the estimation of a 4.5:1.0 potency ratio using UDM during cervical dilation[15], the UDM employed suffers from three fundamental limitations that constrain its utility for robust potency assessment: (1) reliance on sequential dose titration in limited sample sizes (n = 60), which reduces statistical power and precision; (2) exclusive focus on ED50 estimation while neglecting clinically critical ED95 determination; and (3) inherent inability to characterize complete dose-response relationships through mathematical modeling. These methodological constraints significantly compromise the reliability of comparative potency evaluations between anesthetic agents. Our randomized dose-response design overcomes these methodological constraints, quantifying ED95 and calculating confidence intervals for the potency ratio (2.4–9.0.4.0), which directly offer clinicians a range to adjust doses based on patient comorbidities. Furthermore, we chose the successful anesthesia induction (MOAA/S ≤ 1 within 2 min) rather than a single procedural step (e.g., cervical dilation) as primary endpoint, our results offer broader applicability to anesthesia protocols. The 4.1:1.0 potency ratio and favorable safety profile position ciprofol as a transformative option for hysteroscopy. For a 60 kg patient, substituting propofol (2.16 mg/kg × 60 = 129.6 mg) with ciprofol (0.53 mg/kg × 60 = 31.8 mg) could reduce drug volume by 76%, minimizing injection pain and vascular irritation.

The selection of MOAA/S ≤ 1 within 2 min after administration of the initial dose as the primary endpoint was based on established pharmacokinetic profiles demonstrating peak drug effects at approximately 2 min post-injection for both agents [9, 11, 14, 16, 17]. Neurophysiological validation was provided by spectral entropy (SE) monitoring (Supplementary Figure A). At minimum doses (ciprofol 0.2 mg/kg; propofol 1.0 mg/kg), mean SE values remained near baseline (around 90). At maximum doses (ciprofol 0.5 mg/kg; propofol 2.5 mg/kg), SE decreased below 50 by 1.5 min. This dose-dependent SE suppression confirms the appropriateness of the 2-minute assessment window for detecting adequate anesthetic depth corresponding to MOAA/S ≤ 1.

Consistent with previous studies[8, 9, 11, 12], ciprofol’s potency advantage coexists with zero injection pain (0% vs. 34.5%) and reduced respiratory depression (27.6% vs. 55.2%) at doses around the ED50, a dual benefit unachievable with propofol dose escalation in the current study. Ciprofol had a lower incidence of pain during injection and less depression of respiration than propofol [9, 12]. The reason may be that ciprofol exhibits low free concentrations in aqueous solutions, binds more tightly to GABA_A receptors with less inadvertent suppression of vital brainstem respiratory circuits. Our findings confirm that ciprofol’s 4.1-fold potency advantage over propofol is coupled with complete elimination of injection pain and attenuated respiratory depression. Ciprofol’s dual therapeutic advantage, unattainable through propofol dose escalation, stems from its distinct pharmacodynamic profile. Its higher receptor binding affinity reduces required drug volume, while modified phenol structure minimizes vascular irritation [6, 7].

This investigation acknowledges several limitations. Firstly, constrained observation window. The 2-minute post-injection assessment period may inadequately capture peak cerebral drug effects and delayed adverse events (e.g., hypotension, respiratory depression). Future protocols should extend monitoring until complete resolution of pharmacological effects. Secondly, unverified pharmacokinetic peaks. It is not clear whether both drugs have reached peak effect or not. Therefore, the estimated relative potency ratio of 4.1 is specific to the investigation setup and particular context (MOAAS less than 1 within 2 min after injection) in the present study. Thirdly, underutilized neurophysiological data. Although spectral entropy (SE) values were recorded, their exclusion from primary endpoint analysis represents a missed opportunity for mechanistic insight. Fourthly, the study population was aged 18–64 years, and the majority of participants in all groups were in their thirties. Therefore, the study results may not be applicable to the elderly. Finally, statistical power constraints. Our study was underpowered to analyze the dose-clinical effect relationship for each drug such as hypotension because of insufficient observation window or sample size. Extended observation periods and larger cohorts are warranted for robust pharmacodynamic safety profiling.

Conclusions

Ciprofol demonstrated a 4.1:1.0 potency ratio over propofol with superior safety in patients undergoing painless hysteroscopy, supporting its use as an alternative for brief procedures requiring rapid anesthesia induction and recovery.

Abbreviations

MOAA/S

the Modified Observer’s Assessment of Alertness/Sedation

CI

Confidence interval

ASA

American Society of Anesthesiologists

GABA_A

Gamma-aminobutyric acid-A

UDM

Up-and-down sequential allocation method

IV

Intravenous

BMI

Body mass index

SE

Spectral entropy

ECG

Electrocardiogram

NIBP

Noninvasive blood pressure

SBP

Systolic blood pressure

MAP

Mean arterial pressure

RR

Respiratory rate

HR

Heart rate

SpO2

Pulse oxygen saturation

SD

Standard deviation

Appendix

Equation for a standard Hill plot sigmoid curve (Eq. 1):

Equation for a standard Emax sigmoidal curve (Eq. 2):

where y is the response as a percentage, b is the Hill coefficient or Hill slope and ED₅₀ is the dose giving a 50% response.

Substituting for these values from our results into Eq. 2 gives the equation:

Authors’ contributions

YZ helped with collection of study data and manuscript preparation; XiaC helped with randomization, anesthesia management and study conduct; LJ helped with study drug preparation and study conduct; XinC helped with manuscript preparation; XiaoQ helped with study design and manuscript preparation. All authors reviewed the manuscript.

Funding

This study was not funded.

Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The authors declare that the study have obtained approval from the Ethical Committee of Women’s Hospital, Zhejiang University School of Medicine (Hangzhou, China) (no. IRB-20220145-R). Written informed consent was obtained from all patients before enrollment in our study. We confirm that our study complies with the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.