Ethics
The study was designed as a single-center, prospective, randomized-controlled trial. Ethical approval for this study (Ethics Committee of the Affiliated Hospital of Jiaxing University) was provided by the Ethics Committee of the Affiliated Hospital of Jiaxing University (LS2020-298), Jiaxing, China (Chairperson Prof Qh Zhou) on August 1, 2020. This study was conducted following the principles outlined in the Declaration of Helsinki. The study protocol was registered in the Chinese Clinical Trial Register (ChiCTR2000038264, links to registration documents: http://www.chictr.org.cn/showprojen.aspx?proj=59083), The Chinese Clinical Trial Registration date is September 15, 2020 (15/09/2020), and the date of patient enrollment is September 17, 2020 (17/09/2020). All participants provided written informed consent before study enrollment.
Participants and design
Written informed consent, both for the interventions and enrollment in the study, was obtained from all participants. Patients aged between 18 and 80 years, with American Society of Anesthesiologists (ASA) physical status Classes I and II, and scheduled for elective unilateral VATS were screened for enrollment in the study. The operation was expected to be completed at 14:00 every day. The exclusion criteria were patients with shock or coma, abnormal blood coagulation, infection in the planned area of block, severe nerve injury on the side of the limb, history of chronic pain requiring analgesics, psychiatric diseases, radiotherapy, chemotherapy, contraindications to non-steroidal anti-inflammatory drugs, allergy of local anesthetic drugs such as lidocaine and ropivacaine or of general anesthetics, who refused surgical anesthesia, history of previous mastectomy or other thoracic surgery, body mass index (BMI) ≥ 35 kg/m2, and inability to use patient-controlled analgesia (PCA).
Anesthesia application
After shifting to the preoperative area, all patients underwent conventional monitoring procedures including electrocardiography, noninvasive monitoring of blood pressure, and peripheral oxygen saturation measurements. Intravenous access was gained using a 22-gauge intravenous needle, and isotonic saline was infused at a rate of 15 mL kg−1 h−1. Anesthetic management was in accordance with a standard protocol. Anesthesia was induced with pre-oxygenation for 3 min followed by intravenous injection of midazolam (0.05 mg/kg), sufentanil (0.5 µg/kg), propofol (1–2 mg/kg), and cisatracurium (0.15 mg/kg). A double-lumen endotracheal catheter was used for positive-pressure ventilation to maintain the end-tidal carbon dioxide level of 35–40 mmHg.
Anesthesia was maintained using 2% sevoflurane with 50% oxygen, remifentanil (0.5 µg kg−1 min−1), and propofol (100 µg kg−1 min−1). Additionally, cisatracurium (0.15 mg/kg) was administered according to the surgical protocol. Surgery (Unilateral thoracoscopic lobectomy) was implemented via a single 3.0–4.0-cm incision in the fourth or fifth intercostal space of the anterior axillary line as the operation hole by the same surgeon group. The anesthetic dose was adjusted to maintain blood pressure within 20% of the baseline value. An additional dose of intravenous remifentanil (0.1–1.0 µg kg−1 min−1) was injected as needed. If the blood pressure decreased by > 20% from the baseline value, 250 mL of 0.9% (physiologic) saline and ephedrine (0.1 mg/kg) were administered. If the heart rate decreased to less than 50 bpm, atropine (0.5 mg/kg) was administered [15]. At the end of the VATS, the effect of cisatracurium was reversed using neostigmine and atropine as needed [7]. After the surgery, patients were transferred to the postoperative recovery room, where the endotracheal tube was removed. All patients received intravenous granisetron 3 mg upon arrival in the recovery room.
Patient grouping and randomization
After endotracheal intubation, the patients were randomly allocated into three groups based on a computerized randomization table created by a researcher who was not involved in the study. The researcher assigned a random ID to each patient, and a blinded anesthesiologist used this ID while collecting the postoperative data in the surgical ward [9].
Application of block intervention
Following endotracheal intubation, patients allotted to the RIB group were positioned in the lateral decubitus position with the chest on the operating side lying superiorly. The ipsilateral arm was abducted from the chest to move the scapula laterally. The RIB was performed as described previously [8]. A high-frequency (6–12 MHz) linear ultrasound probe (LOGIQ e ultrasonic system, Deutschland GmbH & Co. KG, Solingen, Germany) was placed medial to the medial border of the scapula in the oblique sagittal plane. The landmarks, i.e., the trapezius muscle, rhomboid muscle, intercostal muscles, pleura, and lung, were identified in the ultrasound. Under aseptic conditions, an 80-mm 21-gauge needle was inserted at the level of T5–6 in the ultrasound view. A single dose of 20-mL 0.375% ropivacaine was injected in the interfascial plane between the rhomboid major and intercostal muscles. The spread of the local anesthetic solution under the rhomboid muscle was visualized by ultrasonography.
In patients allotted to the RISS group, a linear ultrasound probe was placed in the sagittal plane at the T5–6 level, just medial to the scapula, to identify the trapezius, rhomboid major, and intercostal muscles. A 21-gauge needle was inserted in the plane between the rhomboid major and intercostal muscles in a cephalad to caudad direction, and 20 ml of 0.375% ropivacaine was injected [8]. Thereafter, the ultrasound probe was moved caudally and laterally to identify the tissue plane between the serratus anterior and external intercostal muscles for the sub-serratus block at the T8–9 level. The needle was advanced from its previous position, and an additional 20 mL of 0.375% ropivacaine was injected [12, 13]. All block procedures were performed by the same anesthesiologist who had administered the RIB and RISS blocks in more than 30 cases before this study. In control group (group C), no block intervention was performed.
Analgesic protocol and evaluation of pain and sensorial block
In the post-anesthesia care unit, all patients received patient-controlled intravenous analgesia (PCIA): 100 μg sufentanil with a total of 100 mL, background dose of 2 mL, self-administered bolus dose of 1.5 mL, and locking time of 20 min. Another blinded anesthesiologist conducted pain assessments at the postoperative 30th min by using the 11-point Numerical Rating Scale (NRS), which ranges from ‘0’ (no pain) to ‘10’ (worst pain imaginable). The patients were transferred to the surgical ward at the end of the 30th min. In the surgical ward, the patients were assessed again at 0.5, 1, 3, 6, 12, 18, and 24 h, postoperatively. If the postoperative NRS score was greater than 3, the analgesia pump was pressed once, and the pain was evaluated after 30 min. If the NRS score continued to be greater than 3, the analgesia pump was pressed again.
Outcome measures
The primary outcome measures were total postoperative sufentanil consumption and NRS scores of patients at different time points in the first 24 h. The secondary outcome measures were the doses of remifentanil and propofol, time to first postoperative analgesic request, and satisfaction score of patients (1–10, whereby 10 is the highest). In addition to these measures, postoperative nausea and vomiting (PONV, which were rated on a four-point verbal scale: none = no nausea, mild = nausea but no vomiting, moderate = vomiting one attack, severe = vomiting > one attack), and block-related complications such as pneumothorax, bleeding, allergy, and local anesthetic toxicity were also recorded.
Sample size
The sample size for this study was calculated using PASS 15 (PASS 15.0 is a powerful sample size and power software of choice for clinical trials, pharmaceuticals and other medical research. It also serves as a pillar for all other areas that require sample size calculation or evaluation.) based on a pilot study with 10 patients in each group. The mean sufentanil consumptions in 24 h were 61.8 ± 6.0 μg in group C, 52.2 ± 4.0 μg in the RIB group, and 51.5 ± 3.5 μg in the RISS group. Assuming an α error of 0.01 (two-tailed) with a power of 0.90, at least 24 participants were needed per group. Considering the potential patient dropout rate, we decided to include 30 patients in each group.
Statistical analysis
Statistical analyses were performed using SPSS v25.0 (IBM, Armonk, NY, USA). The distributions of variables in this study were assessed using the Shapiro–Wilk test, whether the observations were normal or skewed. When the data were normally distributed, they were presented as mean ± standard deviation. Continuous data that yielded non-parametric dispersion were presented as median and interquartile range and were analyzed using the Mann–Whitney U test to assess the differences between groups. One-way analysis of variance (ANOVA) was used to compare the differences in outcome parameters (age, BMI, duration of procedure, duration of anesthesia, remifentanil dose, propofol dose, recovery time, NRS score, NRS dynamic score, time to first postoperative analgesic request, total sufentanil consumption in 24 h, and satisfaction scores) among groups. An independent sample t test was used to compare the differences in outcome parameters (remifentanil dose, propofol dose and satisfaction scores) among RIB and RISS groups. The prevalences of nausea, vomiting, ASA I/II, hypertension, diabetes, surgical incision (location of surgical incision in patients), and limb paresthesia were presented as percentages, and the differences among groups were evaluated using the chi-square test. Pairwise comparison among groups for one-way ANOVA was performed using post-hoc analysis and the Student–Newman–Keuls Q-test. The corrected p value was obtained directly, and the cutoff value was 0.05.