The study was approved by the Ethics Committee of Ondokuz Mayıs University School of Medicine (approval no: 2020/508 19-AKD-158). It was registered on ClinicalTrials.gov (NCT05256953). It is a single-center, prospective, randomized, controlled, parallel-group, and single-blind study. Written informed consent was obtained from all participants for the interventions before including them. The participants were included in the study between January and September 2021.
Patients aged 18–65 years who underwent colorectal surgery, and who had American Society of Anesthesiologists (ASA) physical status classification I-II were included in the study. The exclusion criteria were as follows: history of colorectal surgery excluding diagnostic biopsies, coagulopathy, bleeding disorder, injection site infection, allergy to local anesthetics, pregnancy, or psychiatric disorders (depression, bipolar disorder, schizophreniform disorder, or history of antipsychotic drug use); history of opioid use (longer than 4 weeks); body mass index of > 35 kg/m2; block failure results of dermatomal examination performed after block application; and inability to be contacted via telephone for inquiry about pain scores within 3 months.
After the procedure, the sensory block (T6–L1 dermatomes) was checked by an anesthesiologist independent of the physician who applied it at the level of the bilateral mid-axillary line with a pinprick test (27 G hypodermic needle) applied every 5 min (0 = no sensory block; 1 = the presence of tactile sensation but no pain; 2 = no tactile sensation and pain). ESPB was defined as successful for patients with a sensory block score of 1 and above.
Randomization and blinding
Patients were randomized to the ESPB and control groups, each consisting of 30 patients. Randomization was performed with computer-generated random numbers using Statistical Product and Service Solutions (SPSS version 23.0, IBM, New York, USA). Patient codes were placed in sequentially numbered, opaque, and sealed envelopes by a physician blinded to the study. An independent assistant who did not take part in the study opened a sealed envelope 1 h before the surgery and informed the anesthesiologist about the block method to be applied. These random numbers were also used during follow-up and analysis of patient data. While the investigators and outcome assessors were blinded to the intervention applied, due to the nature of the study, the anesthesiologist who administered the block and the patients were not blinded to the group distribution.
ASA standard monitoring procedures (electrocardiograph and noninvasive arterial pressure and peripheral oxygen saturation measurements) were applied to the patients before the procedure; oxygen support was provided with a simple oxygen mask at a rate of 3 l/min. All patients were sedated by administering 0.02 mg/kg of midazolam. The imaginary line passing through the bilateral spina scapula level of the patients in the sitting position was defined as the T4 level, and it was located by palpation towards the caudal aspect. After taking the necessary sterilization measures, the transverse process of the T9 vertebrae and the erector spinae muscle group was visualized in the parasagittal plane using an ultrasound (USG) (2.5–5 MHz, MyLabFivePortable Ultrasound, UK) convex probe. Two milliliters of 2% lidocaine was injected into the input port of the block needle (21G 100-mm-short beveled needle, Stimuplex Ultra 360®, Braun, Germany). The plane between the erector spinae and transverse process was accessed with the block needle in the craniocaudal direction (in plane). Twenty milliliters of 0.25% bupivacaine was injected following hydrodissection. The procedure was repeated the same way on the other side.
Monitoring by electrocardiogram, capnography was performed, and peripheral oxygen saturation, invasive arterial pressure, and bi-spectral index (Covidien, Minneapolis, MN, USA) were assessed in the operating room. After anesthesia induction with propofol (1.5–2.5 mg/kg) and remifentanil (1 µg/kg IV bolus for 30–60 s, followed by 0.25 µg/kg/min), tracheal intubation was performed with rocuronium (0.6 mg/kg). Intravenous infusion of Ringer’s lactate solution (5–7 ml/kg/h) was initiated in all patients. General anesthesia was maintained with sevoflurane and O2/air (fraction of inspired oxygen: 0.40). Caution was exercised to maintain the depth of anesthesia (BIS 40–60). The remifentanil infusion rate was changed according to the mean arterial pressure to maintain the heart rate within ± 20% of the preoperative values. At the end of the surgery, rocuronium’s effect was reversed with 2 mg/kg sugammadex. For postoperative nausea and vomiting (PONV) prophylaxis, the patients were administered 0.1 mg/kg IV dexamethasone before induction and 1.5 mg IV granisetron 20 min before the conclusion of the case. The patients with five-stage verbal descriptive nausea-vomiting scores of ≥ 2 (0 = no nausea or vomiting; 1 = mild nausea, no vomiting; 2 = moderate nausea, no vomiting; 3 = vomiting once; 4 = vomiting multiple times) during their follow-up in the recovery room were administered granisetron (1.5 mg), and the frequency of antiemetic use was recorded. Itching was monitored using the pruritus visual analog scale (VAS) (P-VAS) (0 = no pruritus, < 4 points = mild pruritus, ≥ 4 to < 7 points = moderate pruritus, ≥ 7 to < 9 points = severe pruritus, and ≥ 9 points = very severe pruritus). Patients with P-VAS of ≥ 4 were considered to have itching and were administered 50 mg IV diphenhydramine.
The VAS score (0 points = no pain, 10 points = worst pain imaginable) was explained to the patients during the preoperative period. In addition, information about the patient-controlled analgesia (PCA) device was provided. The patients were informed that they could request analgesics from the PCA device if their VAS was > 3 at rest in the recovery unit. All patients were administered tenoxicam (20 mg IV) following the induction of general anesthesia and paracetamol (1 g IV) at the end of surgery. During the postoperative period, paracetamol (1 g IV) was administered three times a day at 8-h intervals; tenoxicam (20 mg IV) was administered twice a day at 12-h intervals. The PCA device (BodyGuard 575 Pain Manager, UK) was set so that the bolus requested dose was 20 µg/kg, the lock-out time was 6–10 min, and the 4-h limit was 80% of the maximum accessible dose. Where resting VAS was > 3 despite the PCA request, tramadol (100 mg IV, max. 300 mg/day) was administered as a rescue analgesic.
During the postoperative period, recovery was evaluated in three different states: 1, 3, 6, 12, and 24 h at rest (VASr), during coughing (VASc), and at the moment of deep inspiration (VASi). In addition, in the postoperative 3rd month, the patients were contacted by phone, and their resting/coughing/deep inspiration VAS scores were recorded.
The primary measure was the total morphine consumption within the postoperative 24 h. The secondary measurements were VAS scores at rest, during coughing, and at the moment of deep inspiration during the postoperative 24 h and 3 months, the number of patients needing rescue analgesia, frequency of antiemetic use, intraoperative remifentanil consumption, postoperative first oral intake, first urination, first defecation and first mobilization time, duration of hospitalization, and incidence of pruritus.
Sample size calculation
Preliminary data from our pilot study of 10 patients per group revealed that the mean postoperative 24-h total morphine consumption was 11.0 ± 1.9 mg for the control group and 9.8 ± 1.5 mg for the ESPB group. According to the power analysis with independent samples t-test using IBM SPSS V23, the minimum number of patients to be included in the study according to the confidence interval of 95% (1-α), test power of 80% (1-β), effect size of d = 0.701, and the one-way hypothesis was determined as 26 in a group. Taking into account the possibility of data loss or patient dropout, 35 patients were included in each group.
The data were analyzed with IBM SPSS V23. Compliance with normal distribution was examined with the Kolmogorov–Smirnov test. The chi-squared test was used to compare the categorical data by groups. The Mann–Whitney U-test was used to compare the data that was not normally distributed according to binary groups. Cochran’s Q test was used to compare the categorical data by intragroup time. Friedman test was used to compare the data that were not normally distributed according to the intragroup time. The results of the analysis were presented as mean ± standard deviation and median (Q1–Q3) for quantitative data and frequency (percentage) for categorical variables. For subgroup analysis, the conformity of the data to the normal distribution was assessed using the Shapiro–Wilk test. The independent two-sample t-test was used to compare the normally distributed data of the groups, while the Mann–Whitney U-test was used to compare the non-normally distributed data of the groups. The Friedman test was used for data that were not normally distributed to examine the change in the scale scores over time. The chi-squared test and Fisher’s exact test were used to compare the categorical variables of the groups. The results were presented as mean ± standard deviation (95% CI) and median (minimum–maximum) for quantitative data and as frequency (percentage) for categorical variables. The statistical significance level was p < 0.05.