Study population
This study was approved by the Ethics Committee of the Affiliated Cancer Hospital of Guizhou Medical University (Approval No. FZ2023-06–210), and informed consent was obtained from all patients or their legal guardians prior to anesthesia. Patients scheduled to undergo laparoscopic radical colorectal cancer surgery under ultrasound-guided quadratus lumborum block combined with general anesthesia between January 2024 and February 2025 were enrolled. Inclusion criteria were: aged ≥ 65 years, ASA physical status II–III, and body mass index (BMI) between 18.5 and 27 kg/m². Exclusion criteria included a history of allergy to lidocaine, long-term use of analgesic medications, uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg), severe arrhythmias, severe pulmonary disease, hepatic or renal dysfunction, uncontrolled diabetes mellitus (fasting blood glucose > 10 mmol/L), inability to complete the pain numerical rating scale (NRS) assessment, surgical duration of less than 2 h or more than 5 h, intraoperative blood loss exceeding 800 mL, or postoperative admission to the intensive care unit (ICU). This study was registered with the China Clinical Trial Registry (http://www.chictr.org.cn) prior to patient enrollment (ChiCTR2500097315; Registration Date: [17 February 2025]). This study adhered to the ethical principles outlined in the Declaration of Helsinki and the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines.
Grouping and treatment
Patients were randomly assigned to three groups using a random number table: the low-dose group (L group), the medium-dose group (M group), and the high-dose group (H group). A randomized double-blind design was employed; neither the patients nor the postoperative pain assessors were aware of the group allocations. Lidocaine at different doses was prepared by another anesthesiologist, labeled with randomized codes (L, M, or H). The random number table was computer-generated, with a random starting point selected, and numbers read sequentially from left to right. Each participant was assigned to a group based on the remainder of their random number divided by three: those with a remainder of 0 were assigned to the L group, a remainder of 1 to the M group, and a remainder of 2 to the H group. Grouping information was sealed in opaque envelopes or stored in an electronic system.
All three groups received ultrasound-guided anterior quadratus lumborum block with 60 mL of 0.25% ropivacaine (30 mL per side) performed by the same anesthesiologist. Following induction of general anesthesia and successful endotracheal intubation, continuous intravenous infusion of lidocaine was initiated according to group allocation [Batch number: 20240720, Hubei Tiansheng Pharmaceutical Co., Ltd.]. Patients in the L group received lidocaine at a rate of 1 mg/kg/h until the end of surgery. The infusion rates for the M and H groups were 1.5 mg/kg/h and 2 mg/kg/h, respectively [16], with all other intraoperative management identical to that of the L group.
Anesthesia protocol description
Patients fasted for 8 h and abstained from drinking fluids for 2 h preoperatively. Upon admission to the operating room, a warming blanket was placed on the bed and adjusted to a temperature of 33 °C. Standard monitoring procedures were implemented, and intravenous access was established.
General anesthesia was induced with sufentanil 0.3 µg/kg, propofol 1.5–2 mg/kg, and rocuronium bromide 0.6 mg/kg. Following successful endotracheal intubation, patients were connected to a mechanical ventilator with the following settings: tidal volume 6–8 mL/kg, respiratory rate 12–14 breaths/min, inspiratory-to-expiratory ratio 1:2, inspired oxygen concentration 100%, and oxygen flow rate 2 L/min. End-tidal carbon dioxide (ETCO₂) was maintained between 35 and 45 mmHg throughout surgery. Anesthesia maintenance included target-controlled infusion (TCI) of remifentanil at 1.0–3.0 ng/mL and inhalational sevoflurane to maintain a minimum alveolar concentration (MAC) of 0.8–1.0. Rocuronium bromide 0.3 mg/kg was administered intermittently as needed. Intraoperative fluid management was standardized across all patients. The total fluid volume administered was determined by integrating the following components: (1) Maintenance fluid requirements were calculated according to the Holliday-Segar formula (4 mL/kg/h for the first 10 kg, 2 mL/kg/h for the next 10 kg, and 1 mL/kg/h for each additional kg); (2) The preoperative fasting deficit was estimated as the maintenance rate multiplied by the hours of fasting; (3) Ongoing losses, such as blood loss and urinary output, were replaced milliliter-for-milliliter using crystalloid or colloid solutions as clinically indicated; (4) Third-space insensible losses were estimated at 4–6 mL/kg/h based on the extent of surgical trauma. The initial fluid deficit was fully replaced within the first hour of surgery. Subsequently, a continuous infusion was maintained to cover ongoing maintenance requirements, losses, and third-space sequestration. All fluid administration was guided by continuous hemodynamic monitoring, including arterial pressure and heart rate. The protocol permitted clinician-directed adjustments in response to significant hemodynamic variations.
During both induction and maintenance of anesthesia, HR and mean arterial pressure (MAP) fluctuations were controlled within 20% of baseline values. If necessary, ephedrine, atropine, nicardipine, or esmolol was administered to maintain hemodynamic stability. The target-controlled infusion (TCI) of remifentanil was dynamically titrated according to the patient’s hemodynamic response to surgical stimuli. The goal was to maintain HR and MAP within ± 20% of pre-induction baseline values. The titration protocol was as follows: if HR or MAP exceeded 120% of baseline, suggesting potential insufficient analgesia or anesthetic depth, the remifentanil TCI target concentration was increased within the predefined range (1.0–3.0 ng/mL). Conversely, if HR or MAP fell below 80% of baseline, indicating possible excessive depth or vasodilation, the target concentration was reduced. A stable volatile anesthetic background was maintained using sevoflurane at an end-tidal concentration of 0.8–1.0 MAC to ensure hypnosis and amnesia. Remifentanil adjustments were made complementarily to this baseline to specifically modulate nociceptive responses reflected in hemodynamic changes. In cases where hemodynamic parameters persistently deviated beyond the ± 20% threshold despite optimization of remifentanil and sevoflurane, adjuvant agents were administered as needed: ephedrine for hypotension, nicardipine or esmolol for hypertension or tachycardia, and atropine for significant bradycardia.
Nasopharyngeal temperature was measured, and the warming blanket was adjusted to maintain the nasopharyngeal temperature between 36 and 37 °C. Approximately 30 min before the end of surgery, additional sufentanil 10 µg and tropisetron 4 mg were administered. At the end of surgery, remifentanil infusion was discontinued, the sevoflurane MAC was reduced to 0.3, and the lidocaine infusion was stopped. Extubation was performed once the patient exhibited signs of awakening, including eye opening, clear consciousness, recovery of cough reflex, and restoration of adequate tidal volume, after which the patient was transferred to the post-anesthesia care unit (PACU) for observation.
All patients received postoperative intravenous patient-controlled analgesia (PCIA). The PCIA formulation consisted of sufentanil 100 µg, nalbuphine 60 mg, tropisetron 6 mg, and dexamethasone 10 mg, diluted with normal saline to a total volume of 150 mL. The initial bolus was 3 mL, with a continuous infusion rate of 2.5 mL/h, a patient-controlled bolus dose of 1.5 mL, and a lockout interval of 15 min. When postoperative pain scores exceeded 4 on the NRS scale, an intramuscular injection of diclofenac sodium lidocaine 2 mL was administered.
Outcomes
The primary outcome was the postoperative pain intensity, assessed using the NRS (NRS; 0 = no pain, 1–3 = mild, 4–6 = moderate, 7–10 = severe) at the following time points: upon admission to the post-anesthesia care unit (PACU), at PACU discharge, and at 12, 24, 48, and 72 h after surgery.
The secondary outcomes included: (1) The number of patient-controlled analgesia (PCA) presses recorded at 12, 24, and 48 h postoperatively; (2) Total postoperative opioid consumption. (3) Requirement of intraoperative vasopressors (ephedrine dosage). (4) Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores upon PACU admission; (5) Incidence of postoperative adverse events including nausea, vomiting, tachycardia, hypertension, bradycardia, hypotension, and pruritus, within 48 h.
Sample size calculation
Preliminary experiments indicated that postoperative pain NRS scores did not follow a normal distribution; therefore, a nonparametric method was used for sample size calculation. Using PASS software with the sample size calculation module associated with the Kruskal-Wallis test, the power was set at 0.8 (Power = 0.8) and the significance level at α = 0.05. In the pilot study, 27 patients (9 per group) were enrolled. Shapiro-Wilk tests confirmed that postoperative resting NRS scores at 24 h were not normally distributed. The median (Q1, Q3) for each group were as follows: Low-dose group (L group): 4 (3, 5); Medium-dose group (M group): 3 (2, 4); High-dose group (H group): 2 (1, 3).
Based on preliminary experimental data, the intergroup rank-sum differences were calculated and converted into an effect size indicator, yielding a value of 0.3. Using PASS software, and considering a potential patient dropout rate of 20%, the final calculated total sample size required for this study was 75 cases, with approximately 25 cases allocated to each group. During actual enrollment, to account for the complexity of perioperative variables and to ensure the feasibility of subgroup analyses, 38 patients were ultimately included in each group, resulting in a total sample size of 114 cases. Through strengthened follow-up management during the study period, the dropout rate was controlled to below 5%. The final number of cases completed was as follows: 38 cases in the L group, 38 cases in the M group, and 38 cases in the H group.
Statistical analysis
Data were analyzed using SPSS 20.0 statistical software. Compliance with normal distribution was examined using the Shapiro-Wilk Test. Categorical data are presented as frequence, and quantitative data as mean ± standard deviation or median (Q1,Q3). One-way analysis of variance (ANOVA) with Bonferroni correction was used to compare normally distributed quantitative data among three groups, while the Kruskal Wallis test with Dunn’s correction was used to compare the non-normally distributed data. The chi-square test was used for the comparison of categorical variables among groups. Additionally, repeated-measures ANOVA with post hoc Bonferroni test was employed to compare more than two groups, with group as the between-subject factor and time point as the within-subject factor. P