This study was approved by the Ethics Committee of the Deyang People’s Hospital on January 26, 2022 (No. 2022–04-009-K01). This single-center, double-blinded, prospective, randomized study was registered with China Clinical Trial Registration on 10/11/2021 (ChiCTR2100053073). All male patients were enrolled between March and September 2022, and each patient provided written informed consent before entering the trial.

Patients scheduled for elective laparoscopic radical gastrointestinal cancer surgery during March ~ September 2022 were screened through the surgery scheduling system of Deyang People’s Hospital. Eligible patients were 18–70 years old, American Society of Anesthesiologists (ASA) physical status I to III, scheduled for elective laparoscopic radical gastrointestinal cancer surgery (including Gastric surgery, Right Hemicolectomy, Left Hemicolectomy, Sigmoidectomy, and Rectal surgery) using 14 or 16 French (Fr) Foley catheters inserted. Then, we were extubated in the operating room. Patients were excluded if they had hypermagnesemia risk (chronic kidney disease, primary hyperparathyroidism, hyperaldosteronism, and abnormal liver function), contraindications (myocardial damage, atrioventricular block, and allergy to magnesium sulfate) and taking medications known to interact with magnesium sulfate (lithium intake). Elimination criteria were changing to operation method, stay in ICU after the operation, and the first indwelling catheter was failure.

According to a computer-generated (Microsoft Excel) random number table, participants were randomly assigned at 1:1 ratio to the two groups. The patients were unaware of the group allocation as this assignment was concealed in an opaque and sequentially numbered envelope. An investigator not involved in the trial opened the envelope to the attending anesthetists responsible for preparing the magnesium sulfate or normal saline. All data were acquired by the second investigator blinded to the group assignment. The statisticians and staff were also blinded to the treatment assignments in the ward and PACU.

Standardized monitoring included temperature, 3-lead electrocardiography, SpO2, blood pressure, end-tidal carbon dioxide (ETCO2), train-of-four (TOF) system, and bispectral index (BIS). General anesthesia was induced using midazolam (0.04 mg/kg), sufentanil (0.3–0.5 μg/kg), propofol (1–1.5 mg/kg), and rocuronium (0.6–1 mg/kg). Once the patient was unconscious, urinary catheterization was inserted using 14 or 16 French Foley catheters, and the balloon was inflated with 10 mL of distilled water. Anesthesia was maintained with a continuous target-controlled infusion of propofol (Marsh pharmacokinetic parameters: effect chamber target concentration Ce = 2.0 μg/mL) and additional sufentanil as needed. The degree of muscle blockade monitored by TOF-Watch SX, confirmed TOF count of at least 2. Rocuronium was intermittently administered to maintain muscle relaxation according to the TOF count. The depth of anesthesia was adjusted to the appropriate level according to the surgical requirements, and the BIS was maintained at 40–60. Intraoperative vasoactive drugs were used as necessary to maintain heart rate and blood pressure fluctuations within ± 20% of basal levels, followed by 30 mg of ketorolac and 5 mg of toltestrone 30 min before the end of the surgery. The PCIA device was attached to each patient at the end of surgery, administering 100 μg sufentanil, 10 mg toltestrone, and 90 mg ketorolac in 100 mL of normal saline to deliver 2 mL/h as the basal infusion and 2 mL per demand with a 15-min lockout period. After confirming that the patient was fully conscious (BIS of at least 90) and had recovered from neuromuscular blockade (TOF ratio of at least 90%), the endotracheal tube was removed, and the patient was transferred to the PACU.

In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min immediately after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery, and the control group was administered an equivalent volume of normal saline.

In the PACU and general ward, 2 μg sufentanil was administered if the patient complained of moderate to severe CRBD or postoperative pain (NRS ≥ 4). Then, the patient was reassessed 5 min after drug administration, and 2 mg of morphine was administered as a rescue agent if the patient requested additional analgesia.

The primary outcome was the incidence of CRBD at 0 h after the surgery (on admission to the PACU). The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Other outcomes included remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the NRS score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement.

Magnesium-related adverse effects, such as hypotension, bradycardia, respiratory depression, agitation, shivering, dry mouth, nausea and vomiting, were assessed intraoperatively and at 6 h postoperatively. Hypotension and bradycardia were defined as decrease of mean arterial pressure and heart rate by 20% of baseline value. Depression, agitation, shivering, dry mouth, nausea and vomiting were reported by the staff or patient in a yes or no question.

Sample size calculation was performed using the PASS 15.0 (NCSS LLC., Kaysville, U.T., USA). The current results showed that CRBD occurred in 70% of male patients undergoing laparoscopic radical resection of gastrointestinal cancer (based on our unpublished pilot data). Assuming a rounded 40% rate of CRBD in the magnesium group, we calculated a total sample size of 104 male patients (52 in each group) with a two-sided alpha level of 0.05, a power of 0.8, and a 20% dropout.

The data are expressed as mean ± standard deviation, median (interquartile range, IQR), number (proportion), relative risk (RR), and 95% confidence interval (95% CI). Continuous data were checked for normality using the Shapiro–Wilk test. The continuous normally distributed variables were compared using Student’s t-test; whereas the Mann–Whitney and Wilcoxon tests were used for non-normally distributed variables. Two or more proportions were compared using the chi-square test or Fisher’s exact test as appropriate. Repeated measures ANOVA was used for analyzing the differences between variables over a period. Statistical analysis was carried out using SPSS v26.0 (IBM Corp., Armonk, N.Y., USA).