This was a prospective, observational parallel-cohort trial. The protocol was approved by the Institutional Review Board of Seoul St. Mary’s Hospital Ethics Committee (approval no. KC20OISI0124) on April 29, 2020. The study was performed in accordance with all relevant principles of the Declaration of Helsinki. The study protocol was prospectively registered on a publicly accessible clinical registration site recognized by the International Committee of Medical Journal Editors (Clinical Research Information Service, Republic of Korea; approval no. KCT0005040) on May 20, 2020. Written informed consent was obtained from all patients enrolled between May and July, 2020. The study adhered to Strengthening the Reporting of Observational Studies in Epidemiology guidelines (Additional File 1); a study flow chart is shown in Figure 1.
The inclusion criteria for our study were: male sex, age 19–74 years, prostate cancer stage I or II , patients scheduled for elective RALP, and American Society of Anesthesiologists (ASA) physical status I or II. The exclusion criteria were: a history of allergy to a local anesthetic or opioid drug, coagulopathy (international normalized ratio [INR] >2.0 and platelet count <100.0 × 109/L), hemodynamic instability that required strong vasopressors or a blood product transfusion, and refusal to participate.
We divided the patients into three groups based on patient preference: IV-PCA only (reference group), RSB and IV-PCA (RSB group), and ITMB and IV-PCA (ITMB group).
Patient management in the operating room
The RALP surgical technique and balanced anesthetic management were as described previously ; patient care was standardized apart from the analgesic treatments. The attending anesthesiologist and nurses were aware of the group allocations but were not involved in later patient care or data collection (other than the completion of medical records). The RSB was established immediately after the induction of general anesthesia. An ultrasound probe was positioned transversely on the rectus abdominis muscle, above the umbilicus (Figure 2). Guided by real-time ultrasound, a sterile 22-G Tuohy-type epidural needle was cautiously advanced in-plane (to prevent injury to nearby vessels) from medially to laterally until the tip attained the plane between the lateral side of the rectus abdominis muscle and the posterior rectus sheath. After negative pressure aspiration, 20 mL of 0.25% (w/v) bupivacaine was administered and the block repeated on the opposite side. The ITMB block was placed before the induction of general anesthesia. Each patient received 0.2 mg of intrathecal morphine sulfate and 7.5 mg of bupivacaine via a sterile 25 G Quincke type spinal needle inserted between lumbar vertebrae 3 and 4. The drugs were given via a single injection after cerebrospinal fluid was collected. All patients were allowed access to IV-PCA (1,000 μg of fentanyl, 90 mg of ketorolac, and 0.3 mg of ramosetron). The IV-PCA program featured a 2-mL bolus injection and 0.5-mL basal infusion with a lockout time of 10 min. If a patient suffered acute postoperative breakthrough pain (visual analog scale [VAS] score ≥7), 25 mg of pethidine (an IV rescue opioid) was administered based on the discretion of the attending physicians (in the postoperative acute care unit or ward), who were blinded to group assignment.
Over the first postoperative 24 h, peak pain scores when resting and coughing were assessed using a VAS ranging from 0 to 10, where “0” represented no pain and “10” the worst possible pain; pain severity was classified as mild (VAS scores 0–3), moderate (4–6), and severe (7–10). Cumulative IV-PCA drug consumption and the need for IV rescue opioids were assessed.
Preoperative demographic and laboratory parameters were recorded. Intraoperative findings included surgical duration, hypotension status (systolic blood pressure <90 mmHg for more than 10 min), total rescue ephedrine infusion, total remifentanil infusion, crystalloid fluid infusion, urine output, and hemorrhage status. Postoperative findings included the global quality-of-recovery score on a 15-item questionnaire (the QoR-15) ; the incidences of nausea, vomiting, and pruritus; the Clavien-Dindo classification ; and laboratory variables.
The minimum sample size was based on the difference in cumulative IV opioid consumption on POD 1 between patients who received the RSB and ITMB block, calculated using electronic medical records. A minimum sample size of 27 patients/group was required to afford an α = 0.05 and a power of 0.8. We recruited 30 patients for each group; we assumed a dropout rate of 10%. Data are expressed as means ± standard deviations (SDs), medians with interquartile ranges (IQRs), or numbers with proportions (%), as appropriate. The normality of continuous data distributions was evaluated using the Shapiro-Wilk test. Continuous perioperative variables of the three groups were compared via a one-way analysis of variance or the Kruskal-Wallis test; post-hoc testing employed the unpaired t-test or the Mann-Whitney U test. Perioperative categorical variables were compared among the groups using the Pearson χ2 test or Fisher exact test, as appropriate. Trend testing employed a linear-by-linear association method. Logistic regression analysis was used to derive odds ratios with 95% confidence intervals of the risks (postoperative VAS score peaks ≥7 at rest and when coughing) associated with IV-PCA alone (reference), and the RSB and ITMB block, after adjusting for age, body mass index, diabetes mellitus and hypertension status, and intraoperative remifentanil consumption. All tests were two-sided and a p-value <0.017 was considered significant (multiple comparisons were made). All statistical analyses were performed with the aid of SPSS for Windows (ver. 24.0; IBM Corp., Armonk, NY, USA) and MedCalc for Windows (ver. 11.0; MedCalc Software, Ostend, Belgium).