FormalPara Key Summary Points

Painless hysteroscopy is usually performed under total intravenous general anaesthesia without tracheal intubation, with propofol as the main anaesthetic drug and opioid analgesics as supplementary analgesics.

Our study aimed to identify the median effective dose (ED50) of propofol combined with nalbuphine for painless hysteroscopy.

During hysteroscopy with intravenous anaesthesia, the ED50 values of propofol combined with nalbuphine were 1.729 mg/kg (0.1 mg/kg nalbuphine) and 1.658 mg/kg (0.2 mg/kg nalbuphine).

Increases in the nalbuphine dose did not achieve additional benefits; consequently, we suggest that 0.1 mg/kg nalbuphine is the appropriate dose for hysteroscopy.

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Introduction

Hysteroscopy is a minimally invasive technique that is widely used to diagnose and treat gynaecological conditions [1]. This procedure can be performed in an outpatient setting in clinics, without any type of anesthesia and need of an operating room. However, painless hysteroscopy, which aims to improve the patient's experience and is performed under intravenous general anaesthesia without tracheal intubation, is becoming increaslingly popular. In painless hysteroscopy, propofol is commonly used as the main anaesthetic drug and opioid analgesics as supplementary analgesics painless hysteroscopy [Statistical Analysis

All analyses were conducted using SPSS version 23.0 (IBM Inc., Armonk, NY, USA) provided by the Medical Data Processing Center of the School of Public Health of Anhui Medical University. All quantitative data were tested for normality. Normally distributed variables were summarized using the mean and standard deviation, and they were compared using a t test for demographic data. Non-normally distributed continuous variables were analysed using the non-parametric Mann–Whitney U test. All categorical data were tested using a chi-square test. The ED50, 95% effective dose (ED95) and 95% confidence interval (CI) of propofol were calculated by the probit method (probability unit regression). A P value < 0.05 was considered to be statistically significant.

Results

A total of 61 patients were enrolled and all completed the study. The flowchart of patient enrolment is shown in Fig. 1. There was no significant difference in demographic characteristics between the two groups (Table 1).

Fig. 1
figure 1

Flowchart of patient enrolment

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Table 1 Demographic characteristics of patients
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There was no significant difference in the duration of examination time between the two groups (10.32 ± 5.17 vs. 9.50 ± 4.08 min; P > 0.05) or in the total dosage of propofol administered (158.81 ± 53.13 vs. 144.93 ± 33.76 mg; P > 0.05). The ratio of total propofol dose to anaesthesia duration was similar between the two groups (13.57 ± 2.96 vs. 12.82 ± 2.56; P > 0.05). There was no significant difference in the first dose of propofol maintenance time and anaesthesia recovery time between the two groups (P > 0.05). Compared with group A, the initial dose of propofol and VAS pain score in group B were significantly lower, and the differences were statistically significant (initial dosage 99.79 ± 14.63 vs. 92.02 ± 13.63 and VAS pain score 1.58 ± 0.81 vs. 1.17 ± 0.38; both P < 0.05). There was no statistical significance in the incidence of respiratory depression, nausea and vomiting between the two groups (P > 0.05) (Table 2).

Table 2 Comparison of intravenous anaesthesia outcomes between the two groups
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At T1, there were no statistically significant differences in haemodynamic indexes between the two groups (P > 0.05). In comparison with the values at T1, the SBP in both groups was significantly decreased at T2 (P < 0.05), with the SBP in group B significantly lower than that in group A at this same timepoint (P < 0.05). Also in comparison with the values at T1, the DBP in both groups was significantly decreased at T2, with the DBP in group B significantly lower than that in group A at this same time point (P < 0.05). Similarly, the MAP in both groups was significantly decreased at T2, and the MAP in group B was significantly lower than that in group A at this same time point (P < 0.05) (Table 3).

Table 3 Comparison of haemodynamic parameters at different time points
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The ED50 of propofol determined by the up‐and‐down sequential allocation method was 1.729 (95% CI 1.526–1.856) mg/kg in group A and 1.658 (95% CI 1.359–1.799) mg/kg in group B. The ED95 of propofol determined by the up‐and‐down sequential allocation method was 2.051 (95% CI 1.899–3.331) mg/kg in group A and 2.020 (95% CI 1.849–3.832) mg/kg in group B. There was a significant difference in ED50 and ED95 between the two groups (P < 0.05). The sequential doses of propofol coadministered with nalbuphine for intravenous anaesthesia in hysteroscopy are shown in Figs. 2 and 3.

Fig. 2
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Stepwise dose adjustment of propofol with nalbuphine (0.1 mg/kg) (group A) using the Dixon sequential method. Filled circle represents an effective dose; filled triangle represents an ineffective dose

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Fig. 3
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Stepwise dose adjustment of propofol with nalbuphine (0.2 mg/kg) (group B) using the Dixon sequential method. Filled circle represents an effective dose; filled triangle represents an ineffective dose

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Discussion

Hysteroscopy is an important method for the diagnosis and treatment of uterine diseases. Painless hysteroscopy with propofol alone or combined with a pure μ-receptor agonist (such as fentanyl and sufentanil) has become a popular procedure due to the favourable sedative effect and rapid onset and short duration of action of propofol [6]. Studies have shown that the analgesic effect of nalbuphine on women is significantly stronger than that on men [7], resulting in nalbuphine being favoured by obstetricians and gynaecologists due to the gender analgesic advantage. However, there are few reports on propofol being used in combination with nalbuphine for hysteroscopy. Therefore, it is necessary to determine the ED50 and ED95 of propofol when combined with nalbuphine to provide a reference for rational clinical drug use. The induced dose of fentanyl commonly used in clinical anaesthesia is 1 μg/kg, and 1 mL (10 mg) of nalbuphine is considered to be equipotent to 1 mL (100 μg) of fentanyl [8]. Moreover, some studies have also shown that the recommended dose of nalbuphine in endoscopic examination is 0.1–0.2 mg/kg [11, 12].

There was no significant difference in the HR between the two groups at the T1 and T2 time points, but the SBP, DBP and MAP of the two groups were significantly decreased at T2 compared to T1. The degree of decrease was greater when using 0.2 mg/kg nalbuphine in comparison to 0.1 mg/kg nalbuphine, which contradicted what we originally hypothesized. Previous studies have shown that nalbuphine has no direct effect on the cardiovascular system and has little effect on haemodynamics [13,14,15]. These results may have been due to nalbuphine itself inducing mast cells to release histamine, which further dilates blood vessels and lowers blood pressure, or failure to mask the cardiovascular effects of propofol.

Because increases in the nalbuphine dose did not achieve additional benefits, we suggest that the appropriate dose of nalbuphine for hysteroscopy is 0.1 mg/kg.

One limitation to this study is that the combination of propofol and nalbuphine in painless hysteroscopic fouind to be safe and effective may only work in relatively healthier patients (ASA I or II) as no elderly or patients with other health conditions (ASA III or IV) were recruited to this study.

Conclusion

For safety and effective painless hysteroscopic, the ED50 values of propofol combined with nalbuphine were 1.729 mg/kg (0.1 mg/kg nalbuphine) and 1.658 mg/kg (0.2 mg/kg nalbuphine), and the recommended dose of nalbuphine is 0.1 mg/kg.