Comparison of Propofol-nalbuphine and Propofol-fentanyl Sedation for Patients Undergoing Endoscopic Retrograde Cholangiopancreatography

A Double-blind, Randomized Controlled Trial

Peiqi Wang; Yan Chen; Ying Guo; Jiangbei Cao; Hong Wang; Weidong Mi; Longhe Xu


BMC Anesthesiol. 2022;22(47) 

In This Article


Study Design

This prospective, double-blind, randomized controlled clinical trial was approved by the ethics committee of Chinese PLA General Hospital (S2017-075–02) and was registered in the Chinese Clinical Trial Registry (ChiCTR1800016018,07/05/2018)before its initiation in May 2018. Written informed consent was obtained from all patients. All investigators, including nurses and anaesthetists, received standardized training.

Patient Recruitment and Exclusion

The patients included in this study were those who were scheduled for elective ERCP, aged 18 to 79 years, had a BMI of 18.5 ~ 30 kg.m−2 and were classified as ASA I-III. The exclusion criteria were as follows: (i) clear diagnosis of heart disease (heart failure, angina, myocardial infarction, arrhythmia, etc.); (ii) clear diagnosis of pulmonary disease (asthma, chronic obstructive pulmonary disease, pulmonary embolism, pulmonary oedema, or lung cancer); (iii) central nervous system abnormality; (iv) allergy to the study drugs; (v)pregnancy; and (vi)anticipated difficult airway.

Grouping Design and Study Procedure

The patients were randomly divided into 2 groups, the PN group(propofol and nalbuphine) and the PF group (propofol and fentanyl), by using a computer-generated randomization table. All of the patients were admitted to the hospital at least 1 day before ERCP.

The procedure was performed in the endoscopy suite by 1 of the 3 gastroenterologists in the institution, who had the experience of performing at least 500 ERCP procedures each. An experienced anaesthesiologist administered the drugs, and an anaesthesia resident collected the clinical data. We prefilled 5-ml syringes with either 4 ml of liquid fentanyl (50 μg ml−1) or 4 ml nalbuphine (5 mg ml−1) and labelled them with randomized numbers. In this way, all patients, the anaesthesiologist, the anaesthesia resident and the gastroenterologists were blinded to the group information.

All patients were placed in prone position. They all received midazolam and propofol for sedation and were then monitored for sedation depth using the bispectral index (BIS). Midazolam (0.01–0.02 mg kg−1) was initially administered. Patients in the PN group received 0.1–0.2 mgkg−1nalbuphine and 1–2 mgkg−1 propofol intravenous injection over 30s followed by an infusion of propofol at 0.05 to 0.1 mg (kg min)−1, and patients in the PF group received 1–2 μgkg−1 fentanyl and 1–2 mgkg−1 propofol injection over 30s followed by an infusion of propofol at 0.05 to 0.1 mg (kg min)−1. The BIS index was used to assess the level of sedation, and a value of 40–60 was targeted for the procedure.[20] In cases of an index > 60 or sudden patient movement, propofol 20–30mg + nalbuphine 5mg or propofol 20–30mg + fentanyl 50μg were given in an intravenous bolus to the assigned groups as rescue drugs. The procedure was allowed to start at the discretion of the attending anaesthesiologist.

Baseline vital signs were recorded immediately before the procedure. Oxygen was delivered by nasalprongs at 4Lmin−1 or by an endoscopic facial mask at 4 Lmin−1, and a balanced salt solution at 4mL (kghr)−1 was givenduring the procedure. All patients received BIS (BIS VISTA™ monitoring system, Aspect Medical Systems Inc., Norwood, MA, USA) at 1-min intervals for the first 3min after induction and every 3min thereafter. Heart rate (HR), noninvasive mean blood pressure (NBP), respiratory rate (RR), and oxygen saturation (SpO2) were documented every 5min. The situation regarding surgical interruptions was recorded. A modified Aldrete score of 9 was considered recovery, and the patient was transported back to the ward after meeting discharge criteria. The score of patient movement was marked during the operation as follows: no movement (10 points); slight movement, occasionally(8 points); slight movement, frequently(6 points);severe movement only with the arms and legs (4 points); severe movement with the body and head (2 points). The endoscopist and attending anaesthesiologist assessed the process of the procedure at the end and rated it as (I) satisfactory,(II)indeterminate, and(III) not satisfactory. All of the patients were interviewed by the patient sedation satisfaction assessment tool (PSSI) regarding their experience 1 day after the operation. Adverse effects such as nausea, vomiting, pruritus, polypnea and dyspnoea, pain score(visual analogue score, VAS), etc. were noted. The total dose of the study drug and propofol in each group were calculated.

Hypoxia-related adverse events were described as follows: subclinical respiratory depression (90 ≤ SPO2 < 95% for > 10 s)and hypoxia (SpO2 < 90% for > 10 s). There were two degrees of hypoxia: mild risk (75 ≤ SPO2 < 89%)and severe risk (SPO2 < 75%). It was corrected using the following protocols: (I) opening the airway with the jaw-thrust manoeuvre; (II) placing the nasopharyngeal airway; (III) turning over to the supine position; and (IV) tracheal intubation for mechanical ventilation. The endoscope was removed if hypoxemia could not be corrected. The attending anaesthesiologist provided immediate airway support, and the procedure was resumed or abandoned at the discretion of the anaesthesiologist. Hypotension and bradycardia were treated with intravenous ephedrine 0.1 mgkg−1 and atropine 10 μgkg−1, respectively.

Randomization and Sample Size Estimations

A computer-generated randomizationtable was used for the study centre. The randomization sequence was generated by a research assistant who was independent of the study and did not have contact with the study participants. Randomization was performed using opaque sealed envelopes before the induction of anaesthesia.

In this study, the sample size was estimated based on the incidence of hypoxia (SPO2 < 90% for > 10 s) as the main evaluation index. According to the literature, the incidence of SPO2 less than 90% and over 10s is 42.8% in ERCP when using fentanyl and propofol for sedation.[10,11] It was assumed that the incidence of hypoxemia in the PN group was comparable to that in the PF group. Assuming an α value of 0.025, an a β value of 0.2 and a δ value of 0.15, we needed a sample size of 171 for each group according to PASS 11 (NCSS, LLC., Kaysville, UT, USA) software. Allowing for a dropout rate of 10%, we calculated that a minimum of 380 cases would need to be enrolled. Considering potential loss to follow-up, we increased the sample size of each group to 200 patients.

Statistical Analysis

The data are shown as the mean ± SD or percentage as appropriate. Thet test was used to compare the two groups, and if the data distribution was skewed, the Wilcoxon test was used. The χ 2 test and Fisher's exact test were used to compare the incidence of adverse events between the two groups. A p value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 16(SPSS Inc., Chicago, IL, USA).