The study was designed as a prospective, randomized, double-blinded, clinical trial in accordance with the principles outlined in the Declaration of Helsinki and registered prospectively with the Australian New Zealand Clinical Trials Registry (trial ID: ACTRN12618001334291). The study adheres to CONSORT guidelines. The patients with American Society of Anesthesiologist physical status I–II and aged 18–70 y, were included in the study. All patients were scheduled for an elective unilateral radical mastectomy with axillary lymph node dissection. The patients with coagulation disorders, infection at the injection site, a history of previous mastectomy surgery, chronic analgesic usage, a body mass index ≥35 kg m2, and an inability to use a patient-controlled analgesia (PCA) device were excluded.
Ethics, consent, and permissions
The study was approved by Muğla Sıtkı Koçman University Clinical Research Ethical Committee with the decision number 02–07 and the data were collected in Muğla Sıtkı Koçman University Hospital. Each patient provided written informed consent for the ESP block intervention and participation in the study.
Patient groups and randomization
In the operating room (OR), standard monitoring with electrocardiography, noninvasive blood pressure, peripheral oxygen saturation, and bi-spectral index monitoring (BIS) was performed in all cases, and the patients’ baseline (0 min) data were recorded. All patients received i.v. 0.05 mg/kg− 1 (with a maximum dose of 3 mg) of midazolam for sedation. The patients were then randomly allocated into two groups. A computerized randomization table was created by a researcher who was not involved in the study. For each randomized patient, an anesthesiologist (MKT) took the corresponding sealed envelope from a folder indicating the treatment assigned to the patient and prepared a 0.25% bupivacaine or 0.375% bupivacaine solution in two identical 20 ml syringes. In addition, a 10 ml syringe of isotonic saline was prepared for the hydro-location technique. The first anesthesiologist then passed the labeled syringes to a second anesthesiologist (BA) who was also blinded to the group allocations.
The patients were placed in a sitting position for the ESP block interventions. ESP block interventions were performed similar to a previous study . In the first group (group I), the second anesthesiologist (BA) located the ultrasound probe in a longitudinal orientation at the level of the T4 spinous process, then placed the probe 2–3 cm laterally from the midline. After the identification of the T4 transverse process and overlying trapezius, rhomboideus, and erector spinae muscles, the targeted injection site was anesthetized with 3–4 ml of 2% lidocaine. An 80 mm 21-gauge block needle was inserted using the in-plane technique following the same injection point in the cranial to caudal direction until the tip contacted to the T4 transverse process. When the correct needle tip position was confirmed by hydro-location with 3–5 ml of isotonic saline solution, the anesthesiologist injected 20 ml of 0.375% bupivacaine deep into the erector spinae muscle. In the second group (group II), the same block procedure was repeated with 20 ml of 0.25% bupivacaine solution. Following block procedures, patients were placed in a supine position.
The anesthesiologists (BA and MKT) induced general anesthesia with 2–3 mg/kg− 1 of i.v. propofol, 1 mcg/kg− 1 of i.v. fentanyl and 0.6 mg/kg− 1 of i.v. rocuronium bromide. Following endotracheal intubation, all patients received 4–6% end-tidal desflurane in 2 L of a 40% O2 and 60% N2O mixture for maintenance of anesthesia. The minimum alveolar concentration of desflurane was regulated to maintain a BIS value between 40 and 60. All patients received 4 mg of i.v. ondansetron and 8 mg of dexamethasone for postoperative nausea and vomiting (PONV) prophylaxis. Intraoperatively, i.v. 75 mg of dexketoprofen trometamol was applied in both groups. The OR anesthesiologists applied i.v. fentanyl (0.5 mcg kg− 1) when the hemodynamic parameters of the patients increased more than 20% of the baseline measurements. The inhaled gases were ended at the end of the skin closure and i.v. atropine 0.01 mg/kg− 1 and i.v. neostigmine 0.05 mg/kg− 1 were administered to reverse the neuromuscular blockage. The patients were transferred to the recovery room following extubation, In the recovery room, another blinded anesthesiologist (AIU) followed patients with 11-point Numerical Rating Scale (NRS) to evaluate postoperative pain. The NRS ranges from “0” (no pain) to 10 (the worst pain imaginable). The patients rated their pain intensity during coughing, and their NRS scores were recorded at the postoperative 15th and 30th min. All patients received a patient-controlled analgesia (PCA) device on their arrival in the recovery room. The PCA device was set to administer an i.v. 10 mg bolus dose of tramadol with a 20-min lock-time and no basal infusion. Patients with NRS scores ≥4 received i.v. 10 mg tramadol via the PCA device. In cases where NRS scores remained ≥4 at the 30th min, patients received 25 mcg of i.v. fentanyl as rescue analgesia. Patients who required i.v. fentanyl stayed in the recovery room for 60 min. All other patients were sent to the surgical ward at the postoperative 30th min.
Subsequent pain assessments during coughing were carried in the surgical ward at the postoperative first, second, 12th, and 24th h using the NRS. In cases where a patient had received i.v. tramadol three times in the last hour and still had a pain score ≥ 4, i.v. morphine (4 mg) was administered as rescue analgesia in the ward. At the same time as the pain assessment, the patients were questioned about nausea and vomiting. The severity of nausea was assessed by the patients themselves on a 4-point scale (none, mild, moderate, and severe). If the patients had moderate or severe nausea or vomiting, they received 10 mg of i.v. metoclopromide. The incidence of severe nausea and vomiting were also noted in the nurse care records.
The primary outcome measure of the study was total tramadol consumption 24 h after the operation. The secondary outcome measures were the NRS scores at the different assessment times and intraoperative fentanyl requirements. In addition, postoperative fentanyl requirements, postoperative morphine requirements, intraoperative hemodynamic parameters, the incidence of PONV, and complications related to the ESP block interventions were recorded.
Evaluation of the data
The sample size of the study was calculated using the G*Power program (v3.1.9) based on a preliminary study with 15 patients in each group. At least a 20% reduction in total tramadol consumption in the postoperative 24th h was accepted as clinically significant. The mean tramadol consumption was 142.6 ± 28.34 mg in group I, and it was 196.6 ± 29.38 mg in group II. Assuming an α error = 0.01 (two-tailed), with a power of 0.90, at least 18 participants were needed per group. Considering the possible dropouts, 21 patients were decided to include in each group.
The statistical analysis was conducted using Number Cruncher Statistical System 2007 software (Kaysville, UT, USA). Descriptive variables were assessed using statistical methods (mean, median, minimum-maximum, standard deviation, and ratio), and the Student’s t-test was used for the comparison of parametric variables with a normal distribution between the two groups. For the comparison of parametric variables without a normal distribution, the Mann–Whitney U test was used. Pearson chi-square test and Fisher’s exact test were used for comparison of qualitative data. Three separate generalized linear mixed models were conducted to analyze the effects of group and time on NRS, HR and MAP. NRS, HR and MAP were considered as dependents variables group was introduced as between-subjects variable and time as within-subjects variable. A p value < 0.05 was accepted as significant.