Patients and study design
Patients undergoing elective SILC were enrolled in this study from February 2019 to April 2019 at the Affiliated Hospital of Nantong University. The inclusion criteria were as follows: male and female patients between 18 and 59 years of age with an American Society of Anesthesiology (ASA) score of I or II and a body mass index(BMI) of 18-30 kg/㎡. Patients with preexisting neuropathy, coagulopathy, local skin infection, hepatic, renal or cardiorespiratory failure, local anaesthetic allergy, pregnancy, complications of gallstones with gallbladder perforation, diffuse peritonitis or acute pyogenic cholangitis were excluded. All patients were randomly allocated to four groups: group I, (n=29) patient-controlled intravenous analgesia (PCIA) (sufentanil 1 µg/ml); group II, (n=29) PCIA (butorphanol 0. 08 µg/ml); group III, (n=29) ultrasound-guided RSB (ropivacaine 100 mg) combined with PCIA (sufentanil 1 µg/ml); and group IV, (n=29) ultrasound-guided RSB (ropivacaine 100 mg) combined with PCIA (butorphanol 0.08 µg/ml).
The study was registered prospectively with the Chinese Clinical Trial Registry（reg no.ChiCTR1900020738) and approved by the ethics committee of Affiliated Hospital of Nantong University (approval number: 2018-K067), and written informed consent was obtained.
The primary outcome was NRS scores (0-10) of incisional pain at rest and during cough and visceral pain. Secondary outcomes were the dose of butorphanol and sufentanil, the number of PCIA presses, the length of hospital stay and the incidence of postoperative adverse events.
Randomization and blinding
All patients scheduled for elective, SILC were randomly divided into four groups using a computer-generated random sequence concealed in consecutively numbered, opaque, sealed envelopes, which were opened on the morning of surgery.
In all patients, anaesthesia was induced with intravenous midazolam 0.1 mg/kg, propofol 2 mg/kg, sufentanil 0.5 µg/kg and cisatracurium 0.15 mg/kg. Anaesthesia was maintained with an infusion of 10 mg/ml propofol at 4 mg/kg/h and 50 µg/ml remifentanil at 0.2 µg/kg/min. To ensure an adequate depth of anaesthesia, response entropy indexes were kept between 40 and 60 during the entire anaesthesia period by adjusting the rate of infusion of sufentanil and propofol.
After systemic anaesthesia was induced, in groups III and IV, the probe was transversely placed at the lateral level of the umbilicus. Using the in-plane technique, the needle was advanced until the posterior aspect of the rectus muscle was penetrated. No blood and no gas were drawn back; furthermore, a small volume of saline (＜2 ml) was initially injected to ensure that the needle tip was correctly positioned. When the needle was located between the posterior rectus muscle and posterior sheath, 20 ml of 0.5% ropivacaine was injected bilaterally (Figure 1).
Patients in groups II and IV received an intravenous infusion of 1 mg of butorphanol 30 min before the end of surgery. Those in groups I and III received an intravenous infusion of 10 µg of sufentanil 30 min before the end of surgery.
Vital signs, such as blood pressure, heart rate, oxygen saturation, and electrocardiogram pattern, were recorded during the operation. The operative duration, haemorrhage volume and consumption of remifentanil and propofol were also recorded.
PCIA with a bolus dose of 2 µg of sufentanil, a lock-out interval of 15 min and a maximum dose of 2 µg/h was used for routine analgesia in groups I and III. In groups II and IV, all patients received butorphanol PCIA at a background rate of 170 µg/h and a demand dose of 170 µg every 15 min as rescue analgesia for postoperative pain management. During a preoperative visit, patients were adequately informed about the concept of the NRS and trained how to use PCIA.
All patients were treated by the same experienced anaesthesiologist, who specialized in ultrasound-guided regional anaesthesia and did not participate in the postoperative data collection.
Assessment of postoperative pain and measurements
Postoperative pain after SILC is considered to arise from 2 main sources: incision site (incisional pain), visceral structures (visceral pain). The incisional pain was defined as superficial pain on the abdominal wall, the visceral pain was defined as pain inside the abdomen, which may be deep, dull, and more difficult to localize.
Primary outcome: In both groups, a blinded investigator who was not involved in patient recruitment or the anaesthesia procedure recorded the incisional pain at rest and during cough and the visceral pain using a NRS score (NRS; 0 =no pain; 10 =worst pain) at 2,6,12 and 24 h after the operation.
Secondary outcomes: PONV, somnolence, constipation, uroschesis, pruritus, and respiratory depression were separately assessed by a blinded observer. Butorphanol 1 mg was administered intravenously as rescue analgesia in patients with a NRS score＞3 in all groups. The blinded observer recorded the doses of butorphanol and sufentanil and the number of PCIA presses.
Statistical analysis was performed using IBM SPSS 21. Normality testing was performed using the Levene method. Continuous data (age, BMI, NRS scores, butorphanol consumption, sufentanil consumption in PCIA, duration of the operation, bleeding amount, length of stay, the numbers of PCIA presses, frequency of analgesic request) were presented as the mean ± standard deviation (SD) if they are normally distributed, otherwise, they will be presented as the mean and interquartile range; Categorical data (sex, ASA, adverse events) were expressed as frequency and analyzed by the chi-squared (χ2) test or Fisher exact test. The patient characteristics, duration of the operation, bleeding amount, length of stay, the numbers of PCIA presses, frequency of analgesic request were compared among the four groups by one-way ANOVA，after the equal check of variance, two-two comparisons among the means were done by LSD method. NRS scores of incisional or visceral pain use the means of LSD or Tamhane’s T2 test for unequal variances. P＜0.05 was considered statistically significant. Power Analysis and Sample Size (PASS) software (NCSS, LLC, Kaysville, UT, USA) was used for the power calculation. An ɑ=0.05, n＝29, and absolute NRS reduction of 1 were used to calculate the sample size, after many operations, we find that the power value is above 97%. Thus, 116 patients (29 in each group) met our experimental needs.