Design and patients
Ethical approval for this study was provided by the Research Ethics Committee of Sun Yat-sen University Cancer Center (Chairperson: Prof. Wangqing Peng) on 5th June 2018. The study was registered at a clinical trials registry (www.chictr.org.cn, registered number: ChiCTR1800016790), and was conducted at the Sun Yat-sen University Cancer Center from June 2018 to November 2018. This study was designed and conducted on the basis of the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Patients meeting the American Society of Anesthesiologists (ASA) physical status I to III, aged 18 to 75 years old, scheduled for elective RAPN, and receiving general anesthesia were enrolled in the study (Fig. 1). Exclusion criteria included: patient’s refusal, mental illness, history of alcohol or analgesic dependence, allergy to local anesthetics, severe hepatic dysfunction, coagulopathy, chronic pain, infection at the needle insertion site, and body mass index (BMI) more than 30 kg/m2 or less than 15 kg/m2. Written informed consent was obtained from all patients for this trial. The patients were randomly allocated by a computer-generated randomization schedule into one of the two groups (QLB group and control group). The QLB group received a unilateral QLB after anesthesia induction, and no nerve block was performed in the control group.
A sealed opaque envelope containing a card with the computer-generated allocation number (1 = QLB group, 2 = control group) was opened by an anesthesia assistant with no involvement in the study. Ultrasound-guided QLB was carried out by attending anesthesiologists who had extensive experience with this technique (over 60 attempts). Other anesthesiologists who were blinded to the patient group assignments were responsible for anesthesia management and pain management in postoperative care based on the specified scheme of anesthesia and analgesia. The research assistants who were engaged in the study performed the 48-h postoperative follow-up and recorded the clinical variables.
Anesthesia and analgesia protocol
All patients were seen two days before surgery and were instructed on how to use a patient-controlled analgesia (PCA) device and the use of an 11-point visual analog scale (VAS) for the assessment of postoperative pain: 0 = no pain, ranging to 10 = worst imaginable pain. Prophylactic analgesia was performed the night before the surgery for all patients with celecoxib 200 mg, except for those with contraindications.
Upon arrival in the preparation room, peripheral venous access (20-gauge) was established, and standard ASA monitors were applied. Additionally, each patient received routine continuous monitoring of bispectral index (BIS) and train-of-four (TOF) stimulation. General anesthesia was induced with a target-controlled infusion (TCI) of propofol 3–6 μg/mL and intravenous sufentanil 0.3 μg/kg, and tracheal intubation was facilitated with rocuronium 0.9 mg/kg. A total intravenous anesthesia with TCI propofol and remifentanil was used for maintenance of anesthesia in accordance with BIS 40–60. A neuromuscular blockade was ensured throughout the surgical procedure using rocuronium according to a TOF index for adequate muscle relaxation. After intubation, the lungs were ventilated at 8 mL/kg tidal volume with 0–5 mmHg positive end-expiratory pressure. The frequency was set to keep the end-tidal carbon dioxide within the range of 35–45 mmHg. An infusion of phenylephrine between 0.1–0.4 μg/kg/min was initiated to maintain blood pressure values within 20% of the baseline value, and bradycardia (heart rate < 50 beats/min) was treated with atropine 0.5 mg. Dexamethasone 8 mg combined with tropisetron 5 mg was used to treat nausea and vomiting. A single bolus of sufentanil 0.1 μg/kg and flurbiprofen 50 mg was administered at the start of skin closure. All patients were extubated prior to transport to the post-anesthesia care unit (PACU).
At the PACU, a dose of intravenous morphine 2 mg was administrated for rescue analgesia if the VAS pain score was > 3 and was continued every 15 min until the VAS score fell to ≤ 3. Patients were transferred to the surgical ward when they achieved a modified Aldrete score of ≥ 9 and a VAS score of ≤ 3. All patients routinely received a morphine PCA pump with no background infusion. The PCA pump was programmed to deliver 1 mL bolus doses of morphine (1 mg/mL) on demand with a minimum lock-out interval of 6 min, and a total morphine dose not to exceed 15 mg during any 4-h interval. All patients received regular flurbiprofen 50 mg at 8-h intervals and a dose of intravenous tramadol 50 mg was defined for breakthrough pain if the VAS score was ≥ 6, every h until the VAS was ≤ 3. Antiemetic treatment with intravenous tropisetron was available as needed.
Ultrasound-guided QLB2 technique
All blocks were performed after induction of general anesthesia with the patient in the lateral decubitus position. After local sterilization with povidone iodine, a high-frequency (6–13 MHz) linear array ultrasound probe (Sonosite M-turbo, SonoSite, Inc., Bothell, WA, USA) covered with a sterile sheath was placed above the iliac crest and moved cranially until the three abdominal wall muscles were clearly identified. Then, it was slid medially until latissimus dorsi and quadratus lumborum muscles were confirmed within identical short-axis views. A 22-gauge, short-beveled stimulating needle (B. Braun Melsungen AG, Melsungen, Germany) was used for the single-injection block. The needle tip was inserted in-plane with an ultrasound beam targeting the posterior of the quadratus lumborum muscle. Accurate needle tip position was initially readjusted by injecting 1–2 mL of normal saline for hydrodissection image guidance, and 0.5 mL/kg of 0.375% bupivacaine was injected into the lumbar interfascial triangle behind the quadratus lumborum muscle under real-time ultrasound guidance.
All patients underwent RAPN using a Da-Vinci Si system with 4 to 6 port holes. Demographic, anesthesia- and operation-related parameters were recorded, including sex, age, BMI, height, weight, performance time, surgical duration, and consumption of intraoperative propofol and remifentanil. The primary outcome measure of this study was the VAS scores during movement (coughing or turning the body) at 6 h postoperatively. After surgery, patients were evaluated at 4, 6, 12, 24, and 48 h. The measured variables were VAS scores during rest and with movement at the predetermined intervals; morphine titration consumption in the PACU and cumulative morphine PCA consumption; length of PACU stay; morphine-related side effects including nausea, vomiting, sedation (Ramsay scale > 2), dizziness, hypoxemia (pulse oxygen saturation < 95%), and pruritus; and additionally, hospital stay duration and quality of recovery (measured using a 15-item quality of recovery score (QoR-15)) were also documented.
Sample size calculation and statistical analysis
The sample size was calculated based on data from our pilot study (n = 10). We observed that the VAS score (during movement) at 6 h postoperatively was 4 (±2.0). We considered a 50% reduction in the VAS scores to be statistically significant, and therefore 23 patients per group were required to establish variance tests with α = 0.05 and β = 0.1. Ultimately, data from 56 patients were calculated to account for the anticipated 20% dropout rate.
SPSS software from Windows 19.0 (SPSS, Chicago, IL, USA) was used for statistical analysis. For continuous variables, the Kolmogorov-Smirnov test was used to assess the normality of the data. Continuous variables were summarized as mean ± standard deviation, median and interquartile ranges calculated, and analyzed using the Student’s t test or a Mann-Whitney U test as appropriate. For categorical variables, data of the two study groups were summarized as a frequency, n (%), and the Pearson c2 test or Fisher exact test was performed as appropriate. P < 0.05 was considered statistically significant for all results.