The study is a single-center, randomized, controlled clinical trial with the aim of assessing the possible benefits or disadvantages of propofol combined with different doses of remifentanil anesthesia during gastroscopy. The protocol has been approved by the Ethics Committee of Affiliated hospital of Nantong university, China (Ethics Committee number:2019-K072) and is registered at ClinicalTrial.gov with ID number ChiCTR2000029216. (http://www.chictr.org.cn). This work has been reported in accordance with the guidelines of the Consolidated Standards of Reporting Trials (CONSORT).
The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. The trial flow chart is shown in Fig. 1. The patients were recruited from the gastroscopy clinic of affiliated hospital of Nantong university. All patients who participate in the study must provide their written informed consent.
Gastroscopy clinic of affiliated hospital of Nantong university, Jiangsu province, China.
The inclusion criteria were male patients aged 18–60 years, ASA physical classification I-II, BMI ≤ 30 kg / m2. The exclusion criteria were: coagulation disorder or epistaxis; serious heart, lung, liver or kidney disease; allergy to propofol; patients with recent respiratory tract infection.
Randomization, blinding and sample size calculation
According to a random number table generated by a computer, patients are randomly assigned to receive one of four doses of remifentanil including 0 (control group), 1.25 µg/ml (PR1 group), 2.5 µg/ml (PR2 group) or 5 µg/ml (PR3 group) combined with propofol who undergoing gastroscopy. Random numbers and group allocations are generated with a 1:1:1:1 radio. Outcome assessment and statistical analysis will be performed by independent researchers who are from the affiliated hospital of Nantong university and are blind to the group assignment.
The calculation of the sample size in this research was based on the literature reports related to remifentanil used in gastroscopy. The average cases were about 32 to 42 in each group. Thus, we decided to enroll 50 cases in each group. Considering the possible loss of cases in the study, we recruited a total of 246 patients (Figure. 1).
All patients are fasted for 8 h and no water for 4 hours before gastroscopy. A topical anesthesia of oral cavity and pharynx is performed by gargling 2% lidocanine gel (10g: 0.2 g; Jumpcan Pharmacetutical Group, China). After patients enter into the examination room, the nurse opened the peripheral vein using a 24-G intravenous needle for intravenous anesthesia. After establishing an intravenous access, patient is placed at the lateral position as is the routine practice of our hospital for gastrocopy. Patients in all groups receive oxygen at 2L/min through the cannula for approximately 1 minute before they are sedated with propofol or propofol combined with different dose of remifentanil. A propofol intravenous push strategy, and not an infusion pump, is used, because Riphaus et al demonstrated that bolus and continuous propofol infusion allowed almost indentical good controllability of propofol sedation. The anesthesiologist continually evaluated the depth of sedation with the Ramsay Sedation Scale (RSS). Once the RSS score was > 4, the endoscopist inserted the gastroscope and started the procedure. Intermittent administration maintained the depth of anesthesia (RSS > 4) until the procedure was completed.
Electrocardiogram (ECG), non-invasive blood pressure (NIBP), and pulse oxygen saturation (SpO2) are constantly monitored and recorded in all patients. When hypoxia ( Spo2 < 90% for < 1 min) occurred, the flow of oxygen was increased from 2 to 5L/min, and the airway was opened using the jaw-thrust maneuver at the same time. Mask ventilation or even tracheal intubation was performed when severe hypoxia could not be corrected through the above method. The anesthesiologist dealt with other adverse reactions occurred during the operation if necessary.
Main study endpoint
The main study endpoint was the incidence of hypoxia.
Scondary endpoints and adverse events
These were total dose of propofol, onset time (The time from the beginning of administration to the RSS > 4), awaking time, adverse events including hypotension, hypertension, bradycardia, tachycardia, body movenments, nausea, vomiting, intra-operative aeareness.
All data were analyzed by using the SPSS 23.0 statistical package (IBM, Armonk, NY) and were presented as mean ± standard deviation, median (minimum, maximum; or interquartile range) or percentage. Group comparisons about age, weight, operation time, onset time, awaking time and propofol dosage were analyzed by using one-way analysis of variance (ANOVA). Categorical data were compared by using the chi-squared test or Fisher¢s exact test. A P value of less than 0.05 was considered statistically significant.