Erector Spinae Plane Block Improves the Quality of Recovery and Postoperative Pain Management in Patients Undergoing Breast Surgery Compared to the Control But Not the Sham Block Group: A Randomized Controlled Trial

Background. The erector spinae plane (ESP) block has recently been shown to effectively alleviate postoperative pain and reduce opioid consumption in breast surgery patients. However, data are still limited concerning the quality of recovery in patients following this procedure. Methods. This study was a randomized controlled trial (RCT) performed in a university hospital. We randomly allocated patients to one of three groups: ESP, SHAM, and control (CON). Procedures in the ESP and SHAM blocks were performed ipsilaterally with 0.375% ropivacaine or 0.9% saline (0.4 mL/kg). Our primary outcome was the assessment of the patient’s improvement with quality-of-recovery 40 (QoR-40) a day after surgery. Other outcome assessments included postoperative pain evaluation on the visual analog scale (VAS), 24-hour opioid consumption with patient-controlled analgesia (PCA), time to the rst opioid demand, and global satisfaction with perioperative treatment. the ESP CON than those those the CON group. no statistical difference groups.

Quality of Recovery 40 (QoR-40) is a multidimensional questionnaire addressing many aspects of postoperative improvement [8]. The QoR-40 has been used numerous times to measure patients' recovery after different surgeries [9,10]. In addition, this questionnaire seems to be a reliable tool for assessing other techniques, including regional blocks [11].
Our study aimed to evaluate the quality of recovery in patients undergoing breast surgery. In addition, we measured other outcomes, including postoperative pain severity, opioid consumption, and the time to the rst analgesic demand in this population of patients.

Methods
We conducted the trial after obtaining approval from the Internal Review Board of the Medical University of Lublin (KE-0254/92/2018, chairman Professor M. Olejossy). We registered our study on the ClinicalTrials.gov site on 27/01/2021 with the number NCT04726878 before recruiting patients. Finally, we obtained written informed consent from each patient, and the study was conducted according to the tenets of the Declaration of Helsinki for medical research involving human subjects.

Patients
For eligibility, we assessed adults (≥ 18 to ≤ 80 years old) scheduled for single-side breast surgery due to cancer. We excluded patients unable to give informed consent, who had previously participated in the trial (the second breast or a reoperation on the same side), and who quali ed for surgery on two breasts. We also disquali ed patients with known coagulopathy, allergies to the studied drugs, depression, epilepsy, antidepressant drug treatment, usage of painkillers before surgery, and addiction to alcohol or recreational drugs.
One to four weeks before surgery, patients visited our preanesthetic clinic, where an attending anesthesiologist quali ed them for anesthesia. An anesthesiologist identi ed other participants for our study. A meeting was held for the purpose of screening and a rming the patients' willingness to participate in our trial. A day before surgery, an anesthesiologist who participated in the study discussed with each patient the potential risks and bene ts of taking part in the trial. The patients then veri ed and signed their informed consents to participate in our study. Finally, the anesthesiologist presented and explained the QoR-40 form, the visual analog scale (VAS), and demonstrated the use of the patientcontrolled analgesia (PCA) pump. All patients were informed that they could withdraw from the study at any time.

Anesthesia
We anesthetized the patients participating in the study in a similar manner using fentanyl (Fentanyl, Polpharma S.A., Warszawa, Poland) and propofol (Propofol 1% Fresenius, Fresenius Kabi Deutschland GmbH, Bad Homburg, Germany) to induce general anesthesia. Then, an anesthesiologist inserted a laryngeal mask airway. If the risk of aspiration was high, the anesthesiologist secured the airway with an endotracheal tube. In this case, rocuronium and suxamethonium could be used. We maintained anesthesia with sevo urane and fentanyl. We emerged patients from general anesthesia using oxygen, sugammadex, or neostigmine, as required. An anesthesiologist assessed the patient before transfer to the postoperative care unit, taking vital signs and applying the Richmond Agitation Sedation Scale.

Intervention
After inducing general anesthesia, an anesthesiologist involved in the study opened a sealed envelope containing the patient's allocation. We randomized patients into three groups-the ESP block group (ESP), the sham block group (SHAM), and the control group (CON). We continued general anesthesia in the CON group without modi cation. Participants were unaware of their allocations.
Patients in the ESP and SHAM groups were placed in the lateral position contralaterally for injections (Fig. 1). The anesthesiologist scanned the patient's back to determine the injection site (Fig. 2). After preparing the injection eld, the ESP block was performed at the level of T4, as shown in Figure 1. In the ESP group, we used a 0.375% solution of ropivacaine, 0.4 mL/kg, to a maximum of 40 mL administered on the unilateral side. In the SHAM group, we injected 0.4 mL/kg of normal saline into the ESP space up to 40 mL. After injections, we placed the patients supine to perform the surgery.

Analgesia and postoperative care
Approximately 30 minutes before the end of the surgery, the patient received oxycodone intravenously (IV) at a dose of 0.1 mg/kg. The analgesia regime also included IV Paracetamol, one gram every six hours. In the postoperative care unit, the anesthesiologist initiated the PCA with oxycodone, 1 mg per bolus, with a lockout period of ve minutes. If pain exceeded 40 mm on the VAS, the attending nurse could administer a rescue dose of oxycodone (5 mg twice). Routine care included IV Ondansetron, 4 mg twice daily.

Outcomes
The primary outcome of our study was the result of the QoR-40. We also analyzed parts A and B of the survey. A higher score on the QoR-40 means better recovery following breast surgery. An anesthesiologist who was unaware of participants' allocations assessed the QoR. We hypothesized that QoR-40 scores in the ESP group would be signi cantly higher than in the CON group.
Secondary outcomes included postoperative pain severity, opioid consumption, time to the rst opioid demand, and treatment satisfaction. An attending nurse not directly involved in the study measured pain severity on the VAS at hours 2, 4, 8, 12, and 24 following surgery. We also assessed overall satisfaction with treatment. Satisfaction was presented on a Likert-type scale from one to ve points (very poor, poor, moderate, good, and excellent). Higher scores indicate greater satisfaction. Moreover, we analyzed the impact of the surgery type-partial resection versus breast amputation-on the aforementioned goals.

Statistics
We investigated the normality of the distribution for continuous variables with the Shapiro-Wilk test. We analyzed normally distributed parameters using an analysis of variance (ANOVA). These variables are presented as means with 95% con dence intervals. We used the Kruskal-Wallis test by ranks to compute parameters with non-normal distributions. If the Kruskal-Wallis test results showed statistical signi cance, the Bonferroni correction was applied. Then, a pairwise comparison was performed using the Mann-Whitney U test. These data are presented as medians and interquartile ranges (IQR). Qualitative parameters were compared with Fisher's exact test. The time to the rst demand for oxycodone with PCA was presented as the Kaplan-Meier curve. For this variable, we calculated statistics using the log-rank test. All measurements were performed using Statistica 13.1 software (StatSoft, Tulsa, OK, United States). Randomization was also generated with Statistica software's random number generator by a team member who was not directly involved in recruiting, treating, and assessing patients.
A preliminary study was performed to assess the sample size. The study's primary outcome was the quality of recovery measured with the QoR-40. We compared 14 patients, seven after ESP, and seven controls. The mean results of the QoR-40 were 185 after ESP and 172 in patients without any intervention. The calculated sample size was 11 individuals for each group, power 0.8, and alpha 0.05.
Because three comparisons were necessary, we decided to randomize 75 participants into groups, with 25 individuals in each group.

Results
The study was conducted from February to August 2021 in the surgical department of the university hospital. We assessed 93 patients for eligibility. Ultimately, we analyzed 65 patients (see Fig. 3, Flowchart). Patient demographics are presented in Table 1. All patients participating in our trial were women. Results are presented as means (95% con dence intervals) or n for frequency data. The probability for continuous variables was calculated using one-way ANOVA and frequency data using the Freeman-Halton extension of Fisher's exact test. BMI = body-mass index, CON = control group, ESP = erector spinae group, ETT = endotracheal tube, LMA = laryngeal mask airway, N = number of individuals, SHAM = SHAM group.

Primary outcomes
Patients who received the ESP block scored higher than the CON group on the QoR-40. Moreover, we noticed a difference between the ESP and CON groups for either part A or part B of the QoR-40 ( Table 2). The ESP group scored more points than the SHAM group in part B of the QoR-40 questionnaire. Acute postoperative pain severity was higher in the CON group than in the ESP group at hours 2 (p = 0.012) and 4 (p < 0.01).

Opioid consumption
Postoperative oxycodone consumption (p < 0.01) with the PCA pump and all PCA demands (p = 0.01) were signi cantly higher in the CON group than in the ESP group ( Fig. 4; Table 4). We found no disparities between the SHAM and the rest of the studied groups. Only ve patients required rescue doses of oxycodone-three in the CON group and two in the SHAM group.

Treatment satisfaction
Both patients and an assessor found the satisfaction with treatment better in the ESP group than in the CON group (Table 5).  (Fig. 5). Only three patients, two in the ESP group and one in the SHAM grop, did not use the PCA pump.

Surgery type
In all outcomes in the studied patients, we found no disparities between breast amputation and partial resection (Table 6).

Discussion
The primary hypothesis of our study-patients undergoing breast surgery with the ESP block have better quality of recovery-was con rmed in the results. However, the ESP group achieved better recovery than the CON group, as measured on QoR-40, but not better than the SHAM group. We found a disparity between the ESP group and the CON and SHAM groups only in Part B of the QoR-40 (Table 2).
Patients in the CON group had more severe pain than those in the ESP group, but only in hours 2 and 4 ( Table 3). According to this outcome, there was no difference between the ESP and the SHAM groups or the SHAM and the CON groups. As presented in Table 4, patients after the ESP block used less oxycodone and had fewer PCA demands than the CON group. Moreover, the rst opioid demand was signi cantly sooner in the CON group than in the ESP group. Again, we observed no disparity between the SHAM and the other groups. Finally, the surgical technique, total versus partial breast resection, did not impact outcomes in our study (Table 6).
To our knowledge, the only study in which the ESP block was compared with a SHAM block was by Yao et al. [12]. Moreover, Yao et al. measured the quality of recovery of patients following breast surgery.
However, the authors of this trial used a shorter version of QoR-40, QoR-15. In contrast with our results, they reported a signi cant difference between the two groups in favor of the ESP group, according to each of the primary outcomes, including quality of recovery, pain severity, and opioid consumption. We observed a disparity between the ESP and the CON groups in the current study, but not between the SHAM and the other groups. It is possible that the lack of statistical difference between the ESP and the SHAM groups was caused by the inclusion of a third group in our trial.
Our results concerning postoperative pain severity are consistent with most trials comparing the ESP block with a CON group. The ESP alleviated pain intensity after breast surgery measured with VAS or a numerical rating scale [6,13,14,15,16,17]. However, Aksu et al. did not observe a difference in pain severity between the ESP block and the CON [18]. In this study, the ESP block was performed at two levels; thus, the total volume of injection was divided. This maneuver could change the spread of local anesthetic. As presented in the cadaveric study by Choi et al., a larger injection volume during the ESP block results in a vaster area covered with dye [19].
The results of each study comparing the ESP block to a CON group showed that this regional block reduced opioid consumption in the postoperative period [6, [13][14][15][16][17][18]. However, the PECS block could be even more effective in reducing pain severity and opioid consumption after breast surgery than the ESP block, as presented in studies by Sinha et al. and Altiparmark et al. [20,21]. These results con rmed our previous outcomes in which the additional PECS block was superior to the ESP block alone in patients undergoing mitral/tricuspid valve repair [22].
We did not nd signi cant differences between the ESP and the SHAM groups in the current study. As mentioned above, our study may be underpowered to present disparities between these groups, and more participants would be required. However, it is possible that some pain-relieving action of the ESP block is caused by spreading the uid and separating fasciae. Especially the long-term pain relief in patients following the ESP or other plane blocks cannot be explained by local anesthetic action only [Pirracini 2018, 2019].
Our study has some limitations. First, although we calculated the sample size according to the preliminary results, the studied population was still small. Second, the group was heterogeneous due to two types of surgeries. Third, we did not check the ESP block area with the pinprick technique because the patient was anesthetized generally.

Conclusions
To conclude, the results presented in our study showed the superiority of the ESP block over a CON group in the quality of recovery in patients undergoing breast surgery. Moreover, the ESP block lessened pain severity and reduced opioid consumption. However, we did not prove the advantage of the ESP block over the SHAM group in any studied outcomes. Consent for publication : Each patient who participated in the study was informed that results would be published in a scienti c journal. This piece of information was a part of the informed consent form.

List Of
Availability of data and materials: The data are available from the corresponding author after a reasonable request.
Competing interest: Authors declare no competing interests.     Oxycodone consumption The gure presents postoperative oxycodone consumption administered with PCA. * CON signi cantly higher than ESP. CON = control group, ESP = erector spinae plane group, PCA = patient-controlled analgesia, SHAM = sham block group.