Introduction
Breast cancer is the most prevalent malignancy among women worldwide [1]. Modified radical mastectomy (MRM) is a frequently employed surgery for breast cancer; however, it is often associated with moderate-to-severe postoperative pain [2]. Uncontrolled pain can impede effective coughing and breathing after surgery, potentially leading to complications such as atelectasis and diminished respiratory function [3]. A range of pain management strategies are currently employed after breast surgery, including nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, epidural analgesia, paravertebral blocks, and various interfascial plane blocks, each aiming to optimize postoperative analgesia and improve patient outcomes [4].
Regional anesthesia techniques, such as intercostal nerve blocks, thoracic epidural analgesia, and thoracic paravertebral blocks, have a long-standing history of providing postoperative analgesia after MRM. Although both thoracic epidural analgesia and thoracic paravertebral blocks have been shown to enhance postoperative respiratory function and offer effective pain management, they are associated with potential complications, including intrathecal spread, hypotension, and pneumothorax [5,6]. These concerns, along with various contraindications and technical challenges, have motivated the search for alternative methods. Recently, different types of interfascial plane blocks, each designed for a particular surgery, have emerged and gained popularity. Typically, these methods offer less invasive and simpler alternatives. Notably, the rhomboid intercostal plane (RIP) and serratus anterior plane (SAP) blocks have gained attention for pain management during breast surgery.
The RIP block, as described by Elsharkawy et al. [7] in 2016, provides analgesia for breast surgery by targeting the lateral cutaneous branches of the intercostal nerves from T3 to T9. Several randomized controlled trials have supported its analgesic properties in managing postmastectomy pain [8].
Blanco et al. [9] defined the SAP block in 2013 as an extension of the pectoral blocks. It has been shown to elicit analgesia between the T2 and T9 dermatomes. Subsequent research has demonstrated that the SAP block effectively alleviates acute pain following thoracic and breast surgery and reduces the incidence of chronic pain [10].
Despite ongoing research on the analgesic efficacy of these newer techniques, studies evaluating their impact on postoperative respiratory function are notably lacking, highlighting the need for further investigation. Therefore, this study aimed to evaluate the impact of combining the RIP and SAP blocks on respiratory function after MRM.
Materials and Methods
Trial design
We designed and conducted this single-center, parallel-arm, randomized controlled trial in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. This study was conducted at a training and research hospital between September 2022 and April 2023. Ethical approval was granted by the Muğla Sıtkı Koçman University Clinical Research Ethics Committee, Muğla, Turkey (approval date: October 27, 2021, number: 22/V). The protocol was registered before patient enrollment at clinicaltrials.gov (NCT05547932). This study adhered to the principles outlined in the Declaration of Helsinki, 2013. Patients were seen in the surgical ward the day before the surgery and informed about the study. Written informed consent was obtained from all the patients.
Participants
We enrolled female patients aged 18–65 years, classified as American Society of Anesthesiologists physical status I–II, who were scheduled for MRM under general anesthesia. We excluded patients with existing or previous lung disease, a history of rhinitis or atopic dermatitis, a history of cardiac disease associated with shortness of breath (New York Heart Association class > 2), a respiratory tract infection in the last two weeks, a history of alcohol or substance abuse and chronic opioid use, use of any painkillers in the 24 hours before surgery, active smoking or a history of smoking, body mass index > 35 kg/m2, signs of infection in the area to be blocked, known allergy to local anesthetics, a history of severe psychiatric illness, and an operation time > 180 minutes.
Anesthesia management
Standard intraoperative monitoring was performed in all patients, including electrocardiography, noninvasive blood pressure measurements, and pulse oximetry. After establishing peripheral vascular access with a 20-gauge cannula in the hand, crystalloid infusion was initiated. General anesthesia was induced using intravenous propofol (2 mg/kg), fentanyl (2 µg/kg), and rocuronium bromide (0.6–1.2 mg/kg). After intubation, peripheral nerve stimulation was monitored in all the patients. Anesthesia was maintained with 1 minimum alveolar concentration of sevoflurane in a 2 L/min oxygen-air mixture. The ventilator was set to pressure-controlled volume-guaranteed mode, targeting a tidal volume of 6 ml/kg, maximum peak pressure of 30 cmH2O, respiratory rate of 12–16 breaths/min, and EtCO2 level of 35–45 mmHg. Fentanyl (1 µg/kg) was administered for intraoperative analgesia. A standard analgesia protocol was followed, which included intravenous dexketoprofen (NSAID) 50 mg as an infusion during surgery and tramadol (1 mg/kg) administered 15 minutes before the end of the surgery. All patients received 4 mg intravenous ondansetron for postoperative nausea and vomiting (PONV) prophylaxis. The neuromuscular block was reversed with intravenous neostigmine (0.04 mg/kg) and atropine (0.02 mg/kg). The patients were extubated when the train-of-four (TOF) ratio exceeded 0.9. After extubation, the patients were transferred to the recovery room.
Randomization and blinding
Before surgery, the patients were randomly assigned to the block or control group using a computer-generated randomization table prepared by a professional statistician who was not involved in the study. The allocation was concealed in opaque, sealed envelopes. After tracheal intubation was completed, an anesthesiologist experienced in fascial plane blocks unsealed the envelopes and administered either the RIP and SAP blocks or no block according to the group assignment. The anesthesiologist in the operating room who performed the block procedure did not participate in postoperative data collection. As the patients were under general anesthesia during administration of the block, they remained blinded to their group allocation. The outcome assessors were not provided with any information regarding the treatment plans.
Ultrasound-guided rhomboid intercostal plane and serratus anterior plane blocks
Patients in the block group were placed in the lateral decubitus position with the upper arm crossed over the chest and scapula directed outwards. A high-frequency linear ultrasound probe (6–13 MHz, Sonosite M-Turbo, Fujifilm Inc.) was positioned obliquely on the medial border of the scapula at the T5–6 vertebrae level to visualize the ribs. Once the ultrasonographic landmarks (rhomboid major muscle, fifth and sixth ribs, and intercostal muscles) were visualized, a nerve block needle was directed to the interfascial plane between the rhomboid major and intercostal muscles for RIP block application with 20 ml 0.25% bupivacaine. Subsequently, the ultrasound probe was moved to the mid-axillary line at the level of the third rib to visualize the latissimus dorsi, serratus, and intercostal muscles. The nerve block needle was then guided between the serratus and intercostal muscles for SAP block application with 20 ml of 0.25% bupivacaine. All procedures were performed under sterile conditions.
Postoperative analgesia protocol and pain measurements
We used the numeric rating scale (NRS) to assess postoperative pain levels. Patients provided pain ratings on a scale from 0 to 10, with 0 representing ‘no pain’ and 10 indicating ‘the worst pain imaginable.’ Pain was assessed by an anesthesiologist who was not present in the operating room. Pain scores were evaluated in the post-anesthesia recovery unit at 15 and 30 minutes after surgery and at 1, 2, 6, 12, and 24 hours postoperatively in the surgical ward. Opioid consumption was also recorded at these time points.
After surgery, the patients were transferred to the post-anesthesia recovery unit. After 30 minutes, those with a pain score < 4 and no complaints of PONV were moved to the surgical ward, whereas patients with a pain score ≥ 4 received intravenous fentanyl 50 µg as a rescue analgesic and were reassessed 15 minutes later. If PONV was noted, patients were treated with intravenous metoclopramide (10 mg) administration.
In the surgical ward, patients received intravenous paracetamol (1 g every 8 hours) and an intravenous infusion of 50 mg dexketoprofen every 12 hours. For patients with an NRS score ≥ 4, rescue analgesia with intravenous tramadol 1 mg/kg to a maximum daily dose of 400 mg was administered.
Outcome measures
The primary outcome measure was the difference in forced expiratory volume in one second (FEV1) 2 hours postoperatively. Secondary outcomes included forced vital capacity (FVC), FEV1/FVC ratio, peak expiratory flow (PEF), forced expiratory flow at 25% to 75% (FEF25-75), NRS pain scores at rest and during movement, and opioid rescue analgesia requirements within 24 hours. Additionally, demographic data, comorbidities, operation time, intraoperative fentanyl requirements, and the incidence of PONV were recorded.
On the morning of the surgery, preoperative pulmonary function was assessed using a handheld spirometer (Contec SP10, Contec Medical Systems). Postoperative pulmonary function was evaluated at 2, 6, and 24 hours after surgery. For spirometry measurements, parameters including FEV1, FVC, FEV1/FVC ratio, FEF25-75, and PEF were measured three times at each time point, and the highest values were recorded for each parameter.
Sample size calculation and statistical analysis
Owing to the lack of studies examining the impact of regional anesthesia on respiratory function after breast surgery, we reviewed research involving upper abdominal surgeries, which have been more thoroughly investigated in this context. A difference of approximately 10% in respiratory outcomes was associated with the use of regional anesthesia [11]. According to a study conducted by Jimenez-Tornero et al. [12] in 2020, which evaluated respiratory outcomes following MRM, a 13%–18% difference was expected between the groups. However, as breast surgery is expected to have less impact on respiratory function compared to upper abdominal surgeries, we considered a 10% increase in FEV1 values to be clinically significant.
The G*Power 3.1 software (Faul, Erdfelder, Buchner, & Lang, 2009) was used to estimate the sample size. We initially conducted a pilot study with 10 patients in each group. In this preliminary study, the mean postoperative FEV1 values at 2 hours were 2.18 ± 0.27 L in the RIP+SAP block group and 1.96 ± 0.18 L in the control group. A standardized effect size (Cohen's d) of approximately 0.73 was obtained by calculating the aggregated standard deviation as 0.23 based on these values. The minimum required sample size per group was determined to be 29, using these values and assuming a two-sided alpha of 0.05 and a power of 80% (β = 0.20). We determined that a sample size of 29 patients per group was adequate based on the proximity of the observed effect size to the required threshold (d = 0.75) and the normalization. To enhance the study's power and mitigate the risk of data loss, we enrolled 32 patients in each group.
SPSS software package version 25 (SPSS Inc.) was used for data analysis. The Shapiro-Wilk test was applied to detect normal or non-normal data distributions according to the groups. The NRS values at rest and during movement at 15 minutes, 12 hours, and 24 hours, along with the NRS values during movement at 30 minutes, were non-normally distributed and thus reported as medians with interquartile ranges. Descriptive statistics and percentage frequency values for all variables measured in our study and existing categorical groups were calculated and presented. The t-test was used to calculate the differences in continuous variables between the groups. The Pearson’s chi-square test was used to determine the relationships between categorical variables. The repeated measures analysis of variance (RMANOVA) test was used to observe the distribution between measurements repeated at different times and the interaction effect of the groups. Bonferroni-adjusted post-hoc comparisons were applied following significant RMANOVA results. The results are presented as means, standard deviations, medians, and interquartile ranges, with relevant P values of statistical significance. Statistical significance was set at P < 0.05.
Results
We recruited 69 female patients during the enrollment period. Of these, four were excluded due to noncompliance with preoperative pulmonary function testing and one patient declined to participate. Consequently, 64 patients were randomized and completed the study. Demographic characteristics, intraoperative fentanyl administration, and surgical duration were comparable, and no significant differences in comorbidities were found between the two groups (Tables 1 and 2). No complications related to block performance were observed. The CONSORT flow diagram of this study is shown in Fig. 1.
The block and control groups had similar FEV1 values (1.80 ± 0.51 L vs. 1.74 ± 0.49 L, P = 0.659) and FEV1/FVC ratios (88.06 ± 7.59% vs. 90.34 ± 5.59%, P = 0.176) at 2 hours postoperatively. FVC values were higher in the block group compared to the control group at all time points, with the most significant differences observed at 6 hours (2.21 ± 0.76 L vs. 1.87 ± 0.48 L, P = 0.034) and 24 hours (2.35 ± 0.65 L vs. 1.97 ± 0.53 L, P = 0.014) postoperatively. The block group also had higher PEF (3.79 ± 0.97 L/min vs. 3.21 ± 0.96 L/min, P = 0.019) and FEF25-75 values (2.49 ± 0.75 L/min vs. 2.14 ± 0.51 L/min, P = 0.033) at 24 hours postoperatively. The values at the other time points were comparable; however, repeated-measures analysis revealed a significant increase in FVC, FEF25-75, and PEF values over time in the block group. Furthermore, the differences in these variables between the groups showed an increasing trend over the same period (Table 3).
Table 4 displays NRS pain scores at rest and during movement. Patients who received the RIP and SAP blocks demonstrated clinically significant reduction in pain scores at all time points. The postoperative rescue analgesia demand was higher in the control group than in the block group at all time intervals, except between 12 and 24 hours. More patients in the control group required opioids for rescue analgesia, particularly within the first 6 hours. None of the patients in the block group required opioids after the first hour postoperatively (Table 5).
In the first 24 hours postoperatively, seven patients in the block group and eight in the control group complained of nausea and vomiting. The incidence of PONV was thus similar between the groups (P = 0.768).
Discussion
This study investigated the effects of ultrasound-guided RIP and SAP blocks on the postoperative respiratory function of patients who underwent MRM. The primary endpoint was the difference in FEV1 measurements between the groups 2 hours postoperatively. Contrary to expectations, no significant differences were observed in FEV1 values. However, our secondary outcomes revealed noteworthy improvements in FVC, PEF, and FEF25-75 in the block group, indicating a beneficial effect on respiratory function. Additionally, patients in the block group reported lower postoperative pain scores and reduced opioid consumption.
Recent studies investigating the impact of fascial plane blocks on respiratory function have reported conflicting results. Adhikary et al. [3] conducted a retrospective study on the effects of the erector spinae plane (ESP) block in patients with multiple rib fractures and demonstrated an enhancement in inspiratory capacity, lower levels of pain, and reduced opioid requirements among those receiving the block. Notably, the incentive spirometry volume showed an average increase of 545 ml (95% CI [319, 770]) in the first 24 hours. In two separate studies, the use of bilateral oblique subcostal transversus abdominis plane and ESP blocks led to better preservation of FEV1 and FVC at 2 and 24 hours after laparoscopic cholecystectomy, which was attributed to enhanced analgesia [13,14].
As pain is thought to negatively affect respiratory function, effective pain management is expected to improve this condition [15]. However, the correlation between spirometry measurement parameters and pain scores may not always be evident because various factors can affect respiratory function. Despite the studies mentioned above indicating an improvement in FEV1 with better pain relief, some studies failed to show a correlation between FEV1 and overall pain scores. Mostafa et al. [16] evaluated the effects of the ESP block on perioperative analgesia and pulmonary function in patients undergoing laparoscopic bariatric surgery. Although they noted a reduction in postoperative pain scores and morphine consumption in the ESP block group, no differences in pulmonary function (FEV1, FVC, and PEF) were observed. The authors attributed these findings to obesity and the development of atelectasis due to general anesthesia in the supine position. In a recent study examining the impact of the subcostal quadratus lumborum block on pulmonary function recovery following gastrectomy, Li et al. [11] reported no significant change in FEV1 despite higher FVC values in the block group.
Similarly, in our study, we did not find a statistically significant difference in the FEV1 values. Nevertheless, notable improvements were observed in other spirometry assessment parameters, such as FVC, FEF25-75, and PEF, indicating a potential advantage for respiratory recovery after surgery. The observed decline in FEV1 and FVC compared to baseline in both groups, along with the normal FEV1/FVC ratio, indicated a restrictive breathing pattern, as anticipated for this type of surgery. Typically, this is caused by a cephalad shift of the diaphragm, a decrease in respiratory muscle tone, and reduced functional residual capacity due to general anesthesia, along with compressive dressings that reduce the movement and diameter of the chest wall [12,17,18]. We did not perform chest radiography or computed tomography after surgery to identify possible postoperative complications such as atelectasis, pleural effusions, or minor pneumothorax. These conditions may have influenced the spirometry assessment, leading to similar FEV1 values. However, these tests were unnecessary because none of the patients exhibited oxygen desaturation or any signs of respiratory compromise. Iwabe et al. [19] demonstrated that pain processing, particularly acute pain, fluctuates with breathing, and that pain is gated within the central nervous system during expiration via parasympathetic pathways. Consequently, a difference in pain perception arises between inspiration and expiration, with weaker pain experienced during expiration. Thus, the difference in pain between the groups in our study could have been affected by breathing, resulting in nearly similar pain experiences during expiration, despite the block group having better overall pain scores. This may explain why the FEV1 values did not differ between the groups, as FEV1 primarily depends on expiratory forces. However, existing evidence on this topic is limited and requires further investigation.
Vital capacity depends on achieving full inspiration followed by maximal expiration. Previous research has indicated that better pain management is associated with improved postoperative inspiration. We believe that the observed increase in FVC among patients who received these blocks was due to the superior analgesia provided by the blocks [3]. The role of FVC as a key parameter in evaluating respiratory function and its strong correlation with postoperative pulmonary complications, such as atelectasis, highlights its clinical importance [20].
Additionally, we observed that both FEF25-75 and PEF values improved by 24 hours postoperatively in the block group. FEF25-75 is valuable for diagnosing lung conditions (as opposed to chest wall or muscular pathologies) because it is less influenced by effort or muscle strength than other spirometric values; as it is mostly on the effort-independent portion of the flow-volume curve, its relevance in this study is limited [21]. The difference in outcomes is most likely attributable to the inability of patients in the control group to achieve a higher vital capacity. FEF is highly dependent on the lung volume. In cases without airway obstruction, reductions in FEF25-75 mainly arise from decreased lung volume rather than airway disease [22]. Although FEF25-75 is not a direct indicator of improved postoperative respiratory function, it provides indirect insights into other respiratory parameters, such as FVC, as explained here. Thus, the observed increase in FVC over time in the block group likely contributed to the upward trend in FEF25-75 values.
The RIP block was first introduced by Elsharkawy et al. [7] in 2016. Numerous randomized controlled trials, along with systematic reviews and meta-analyses, have subsequently demonstrated the analgesic efficacy of the RIP block in breast surgery [8,23]. Similarly, the SAP block, which predates the RIP block, has also been shown to effectively relieve pain in patients undergoing breast surgery [10,24]. Consistent with the growing body of evidence, our results indicated that the RIP and SAP blocks were associated with lower pain scores both at rest and during movement than the control group at all time points. The requirement for opioid rescue analgesics was also significantly lower in the block group during the initial 6 hours postoperatively. However, no notable differences in the need for rescue analgesia between the groups were found after this period, as the pain scores gradually decreased over time in both groups. To achieve prolonged postoperative pain relief, applying perineural dexamethasone or administering continuous local anesthetic infusions through catheter placement within the fascial plane are considered viable options. A continuous RIP block has been demonstrated to extend analgesia for up to 48 hours and enhance the quality of recovery in patients undergoing thoracoscopic procedures [25,26]. Likewise, continuous local anesthetic infusions and perineural dexamethasone have been shown to prolong analgesia with the SAP block [27,28]. Additionally, intermittent bolus infusions with the SAP block have been linked to improved pulmonary function and reduced postoperative pulmonary complications after thoracic surgery [29].
As both the RIP and SAP blocks are effective approaches for pain management in breast surgery, their simultaneous application may offer enhanced analgesic coverage and an easy approach to pain management. Theoretically, the RIP block offers analgesia spanning the T3 to T9 dermatomes in both the anterior and posterior aspects of the hemithorax and has been reported to provide broader analgesic coverage than the SAP block. However, because the block does not reach the T1–2 level, it cannot relieve axillary pain arising from axillary lymph node dissection [30–32]. A cadaveric study conducted by Biswas et al. [33] demonstrated that performing an SAP block at the T3 level stained the axillary region in most cadavers. Consistent with this, the SAP block has been used in combination with other blocks to cover the sensory blockade of the axillary region during breast surgery [34,35]. In this study, we employed both techniques concurrently for two reasons. First, we ensured analgesic coverage of the axillary region. Second, because the blocks were performed under general anesthesia, assessing block success was not possible; therefore, in the case of failure of one block, the patient benefited from the effect of the other block. Additionally, because both block procedures were performed with the patient in the lateral decubitus position, repositioning was not required.
Although differences in pain scores and opioid consumption were found, the incidence of nausea and vomiting was similar between the groups. We concluded that this was due to the prophylactic use of ondansetron in all the patients.
Our study has some limitations. First, we did not perform any dermatome analysis to assess the effectiveness of the blocks. However, in the earlier stages it was not possible as the patients were under general anesthesia. Second, we did not include a sham block group, which would have strengthened the validity of our findings. Additionally, we did not assess sedation levels resulting from opioid administration. Given that the control group received higher doses of opioids, the resulting respiratory depressant effects may have contributed to the differences observed in the spirometry measurements. Although we conducted a power analysis before the study, our sample size was relatively small; therefore, larger multicenter trials are necessary to achieve more precise and generalizable results.
In conclusion, this study failed to meet the primary endpoint of demonstrating a significant difference in FEV1 values. However, the analysis of secondary outcomes revealed notable improvements in FVC, PEF, and FEF25-75, indicating a potential positive impact on respiratory function. The combination of RIP and SAP blocks for pain management after MRM also resulted in lower pain levels and reduced opioid consumption compared with the control group. These findings highlight the need for further large-scale studies to validate these effects.
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