Study design and participants
This was a single-centre, prospective, randomized controlled clinical trial that included patients who underwent elective painless gastrointestinal endoscopy from November 2023 to December 2023 at the Gastrointestinal Endoscopy Center of the First Hospital of Lanzhou University. One hundred and sixty-six patients were deemed eligible and subsequently enrolled in the study. The inclusion criteria were as follows: aged between 18 and 75 years, an American Society of Anaesthesiologists (ASA) classification I to II, a Mallampati classification I to II, a body mass index (BMI) between 18 and 30 kg/m2, and an expected painless gastrointestinal endoscopy duration ≤20 minutes. The exclusion criteria were as follows: severe heart or lung disease or abnormal metabolic disease of the liver or kidneys; gastrointestinal obstruction or gastric dyskinesia; narcotic analgesic abuse, sedative overuse or chronic use of benzodiazepines; hypersensitivity to emulsions, opioids, or benzodiazepines; and a procedure time >20 min.
Randomization and blinding
All eligible patients were randomly divided into two groups, the propofol control group (Group P) and the RT group (Group R), using a random number table generated by SPSS 27.0 software in sealed envelopes. Participants, clinicians (excluding the anaesthesiologist), and investigators who were responsible for data collection and follow-up were blinded to the study group allocation. Follow-ups were completed within 48 hours after surgery.
Anaesthesia and interventions
All patients were prohibited from drinking water for 2 h and fasted for 8 h before the operation, bowel preparation was completed 6 h before the operation, and surface anaesthesia was induced with 10 ml of Dyclonine Hydrochloride Mucilage 10 min before the operation. Prior to the procedure, the peripheral venous channel was established, a dental pad was inserted, and oxygen was administered via a nasal cannula at a rate of 2 to 4 L/min. The patient was positioned in the left lateral decubitus position, and SBP, DBP, MAP, HR, and SpO2 were continuously monitored using a multifunctional monitor (Model: uMEC6, Shenzhen Mindray Biomedical Electronics Co., Ltd.).
All patients were injected intravenously with 7 µg/kg alfentanil (Yichang Renfu Pharmaceutical Co., Ltd., batch number: H20203055) for ≥30 s. Subsequently, Group P was injected intravenously with 1.5 to 2.0 mg/kg of propofol medium and long-chain fatty emulsion (Jiangsu Yingke Bio-Pharmaceutical Co., Ltd., batch number: H20203504) for >30 s. Group R was intravenously injected with 0.2 mg/kg of RT (Jiangsu Hengrui Pharmaceutical Co., Ltd., batch number: H20190034), and the injection was completed within 1 minute. The procedure commenced when the patient's modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale score was ≤1 [10]. The procedures were performed by senior gastroenterologists with more than 3 years of experience in performing gastroscopy followed by colonoscopy. In Group P, if any of the patients moved or made obvious swallowing movements during the procedure, 0.5 mg/kg of propofol was added each time, and, in Group R, 3.0 mg of RT was added each time until the patient no longer moved or made obvious swallowing movements, and the depth of sedation was maintained intraoperatively at a MOAA/S scale score ≤1. In Group R, if the patient was unable to finish the gastrointestinal procedure after 2 consecutive additions of medication for 3 min and had a MOAA/S scale score >1, 0.5 mg/kg of intravenous propofol was administered for remedial completion of the procedure. In this case, the interval between each two drug additions was at least 2 min, and no more than 5 drugs were added within a 15-min period.
If hypotension (SBP <90 mmHg, MAP <60 mmHg, and MAP or SBP decreased by more than 20% of the basal value) occurred during the procedure [11], 6 mg of ephedrine (Northeast Pharmaceutical Group Shenyang No. 1 Pharmaceutical Co. Ltd., batch number: H21022412) was injected intravenously. If bradycardia (HR below 50 bpm or a decrease of more than 20% from baseline)occurred, 0.5 mg of intravenous atropine (Suicheng Pharmaceutical Co., Ltd., batch number: H41021257) was given. If hypoxemia occurred (SpO2 <90%), the flow of inhaled oxygen was increased, and the lower jaw was supported. If necessary, a mask can be used to assist breathing or to perform mechanical ventilation with endotracheal intubation.
Outcomes
The primary outcomes of the trial were perioperative haemodynamic variables, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and SpO2 preoperatively (T0); after induction of anaesthesia (T1); at the time the gastroscope passed through the oropharynx (T2); 3 min (T3), 5 min (T4) and 7 min (T5) after T2; at the end of surgery (T6); and at the time when patients successfully awakened (T7). The secondary outcomes included induction time (MOAA/S scale score ≤1); awakening time (time from the end of drug administration to awakening); patient and operator satisfaction scores (using the visual analogue scale scoring method [12]); and incidence of adverse events, including drug injection pain, hypoxemia, hypotension, bradycardia, limb movement, hiccups, postoperative nausea and vomiting, and the 4 times or more drug additions.
Sample size calculation
Based on the results of our preliminary experiment, we calculated that the incidence of hypotension was 40% in Group P and 17% in Group R. In the case of 1-β=0.9 and α=0.05 (two-sided test), the sample size was calculated to be 150 patients using PASS15.0 software. Considering a 10% dropout rate, 166 patients were enrolled.
Statistical analysis
All the statistical analyses were performed using SPSS software (v.27.0). The Shapiro‒Wilk test was used to verify the normality of the data. Normally distributed data are expressed as the means±SDs. The independent sample t test was used for comparisons between groups. Repeated measures analysis of variance (ANOVA) was used to analyse the repeated measures data at different time points. Nonnormally distributed measurement data are expressed as the median (quartile) [M (Q1, Q3)], and comparisons between groups were made using the nonparametric Mann‒Whitney U test. Count data are expressed as cases (%), and comparisons between groups were made using the c2 test or the continuous corrected c2 test. Subgroup analyses were assessed using logistic regression models. Differences were considered statistically significant if the P value was < 0.05.