Breast cancer has overtaken lung cancer as the most commonly diagnosed malignancy and is the leading cause of cancer-related death in women (1, 2). During the past recent years, various therapies emerged in the era of breast cancer. Breast cancer is a heterogeneous disease in which genetic and environmental factors are involved (3). Despite that the breast cancer age-standardized mortality rates have decreased by 2%–4% per year since the 1990s (4), the incidence of breast cancer was 11.7% in total new cases in 2020, both sexes and in all ages (5). Breast cancer treatment methods include surgery, radiotherapy, chemotherapy, hormone therapy, targeted therapy, and immunotherapy (6). Surgery is the only possible cure for breast cancer, so surgical resection of the tumor is the preferred treatment for early breast cancer (7, 8).

The incidence of acute postoperative pain (APP) is high in breast surgery, and opioids are the most commonly used drugs to treat APP. However, they are not without systemic side effects, which may increase comorbidities (9). Although there is no evidence that perioperative pain management reduces patient mortality, perioperative pain might influence the oncological outcome in major tumor resection surgery (10, 11).

There are some local or regional nerve blocks in breast cancer performed as core components of multimodal analgesia and enhanced recovery after surgery (ERAS) (12), including thoracic epidural (13), interscalene brachial plexus (14), paravertebral (15), pectoral nerve blocks (16, 17), and erector spinae plane block (18). Ultrasound-guided serratus anterior plane block (SAPB) is a new analgesic technique applied to the clinic proposed by Blanco (19); it is a block in which local anesthetic is deposited within an interfascial plane either superficial or deep into the serratus anterior muscle at the mid-axillary line (20). Some clinical trials reported that both superficial and deep SAPB provided effective blockade to alleviate the pain after modified radical mastectomy for breast cancer (21–23), but Edwards et al. suggested that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB (24). In fact, despite the use of long-acting local anesthetic agents, the patient’s pain cannot completely be eliminated due to the short duration of anesthesia. Dexmedetomidine is a highly selective alpha-2 adrenal receptor agonist (25); as an adjunct to local anesthetics, the duration of peripheral nerve block can be prolonged. Notably, dexmedetomidine assisted with local anesthetics has been reported to accelerate the onset of action and prolong the duration of block (18, 26, 27). However, to the best of our knowledge, there are no reports on the efficacy and safety of dexmedetomidine combined with local anesthetic in dSAPB. The purpose of this study was to compare the efficacy of dexmedetomidine combined with dSAPB in breast cancer surgery.

The CONSORT 2010 flowchart is shown in Figure 1 . Between May and November 2021, we screened 88 potential participants who planned an elective unilateral modified radical mastectomy under general anesthesia. Based on inclusion criteria, six participants were deemed ineligible, and two declined to participate. A total of 80 participants participated in the trial. After randomization, four patients in the dSAPB with ropivacaine group and three in the dSAPB with DEX plus ropivacaine group were excluded for protocol violation. Therefore, data from 73 patients were used in the final analysis. Patient statistics and operation time were similar between the two groups ( Table 1 ).

The global QoR-15 scores are shown in Figure 2 . The global QoR-15 scores were significantly higher 24 h postoperatively (better recovery) in the dSAPB with ropivacaine plus DEX group than in the ropivacaine group (estimated median difference: 4; 95% CI 1–6, p=0.016).

Preoperative dSAPB administration of 0.375% ropivacaine with DEX reduced acute VAS pain scores at rest at 12th hour, exercise at 12th and 24th hour after surgery (both p < 0.05, Table 2 ). There was no significant difference between resting (p =0.125) and exercise (p =0.104) 48 h after surgery. The dSAPB of 0.375% ropivacaine with DEX group had lower cumulative consumption of opioids (sufentanil) 24 h after surgery compared with the ropivacaine group (median, 14 μg; IQR 12–15, compared with median, 14 μg; IQR 12–17; p=0.022). The median difference between the dSAPB with DEX group and the ropivacaine group was −2 μg (95% CI -2 to 0, p = 0.022).

As shown in Table 2 , the incidence of PONV 24 and 48 h after surgery was 6 (16.2%) in the dSAPB of 0.375% ropivacaine with DEX group vs. 11 (30.6%) in the ropivacaine group, and 5 (13.5%) in the dSAPB of 0.375% ropivacaine with DEX group vs. 8(22.2%) in the ropivacaine group, and the difference was not statistically significant (p =0.147, p =0.331, respectively). Dizziness occurred in three and four patients in the dSAPB of 0.375% ropivacaine with the DEX group and the ropivacaine group, respectively.

Consistent with the recent focus on functional recovery, rather than simply measures of postoperative opioid consumption and pain scores (33). Our study demonstrated that the combination of dSAPB of 0.375% ropivacaine with DEX improves the QoR-15 compared with ropivacaine alone, although these improvement differences do not amount to 8, and maybe no obvious clinical significance. Therefore, we believe these differences will become more pronounced and biases will be avoided as more people are enrolled. Furthermore, participants in the dSAPB of 0.375% ropivacaine with DEX group met the superior pain relief in the early postoperative period, reducing the postoperative cumulative opioid consumption. No dSAPB -related adverse events (eg, local anesthetic toxicity, pneumothorax, bleeding or infection) were observed in the study. Taken together, these findings may still indicate that preoperative administration of dSAPB of 0.375% ropivacaine with DEX may be a useful intervention to aid recovery following breast cancer surgery.

Recovery after surgery and anesthesia is a multidimensional, inter-related, and complex process that involves many areas beyond the scope of postoperative pain (34). QoR-15 is a recently developed patient-reported outcome measure of the quality of postoperative recovery. It was developed from the QoR-40, which has been widely used and validated as a measure of the quality of postoperative recovery (35). Compared to QoR-40, QoR-15 has the same psychometric properties but is more feasible to use (28). QoR-15 is a validated quality assessment tool that can evaluate the efficacy of the post-surgical intervention on QoR-15 from a patient’s perspective (36). Meanwhile, postoperative pain remains a challenge for breast surgery patients (37); strategies to limit pain are increasingly being elaborated. Regional anesthesia technique has provided excellent postoperative analgesia and improved the quality of recovery after surgery (12). The recent emergence of ultrasound-guided regional anesthesia techniques for breast surgery includes thoracic paravertebral block, vertical ridge plane block, and thoracic nerve block, etc. provides an alternative to thoracic epidural/paraspinal block for postoperative analgesia (38). As a result, implementing patient-centered outcomes has been proposed by healthcare organizations in several countries to improve the quality of care. In this study, preoperative ultrasound-guided single-injection dSAPB of 0.375% ropivacaine plus DEX resulted in a change of 4 in QoR-15 score, indicating relevant improvement in patients’ early postoperative health status.

Dexmedetomidine has an anti-sympathetic effect that activates the vagus nerve and reduces plasma catecholamine levels, thereby providing stable hemodynamics. The analgesic effect of dexmedetomidine is the result of multiple mechanisms. A previous study suggested that the addition of dexmedetomidine to ropivacaine for sciatic nerve block in rats not only prolonged the duration of sensory and motor block of the sciatic nerve but also markedly alleviated ropivacaine−induced neurotoxicity by decreasing caspase−3−dependent sciatic nerve cell apoptosis (39). Intrathecal dexmedetomidine (5 μg) reduced the ED of intrathecal hyperbaric ropivacaine by approximately 18% for cesarean section in healthy parturients under combined spinal-epidural anesthesia (40). Lower postoperative pain scores and reduced perioperative opioid consumption are thought to be important causes. The mechanism of dexmedetomidine is mainly to activate sodium and potassium pumps to enhance membrane hyperpolarization (18). The analgesic effect of dexmedetomidine around the nerve is due to the enhancement of the cation channel activated by hyperpolarization, which prevents the neuromembrane potential from recovering from hyperpolarization to discharge in the resting state (41). Compared with placebo, dexmedetomidine prolonged sensory block time of ulnar nerve by 60% and systemic dexmedetomidine extended sensory block time by 10% (42). Therefore, local anesthetics combined with dexmedetomidine can enhance the inhibition of nerve conduction, and its analgesic effect is superior to that of local anesthetics alone.

The analgesic effect of postoperative single nerve block remains to be further elucidated due to the unsatisfactory and difficult management of indignant peripheral nerve catheter (43). Ropivacaine is a long-acting amide local anesthetic that is thought to be better at separating sensory and motor effects and less cardiotoxic (44). However, the time of using ropivacaine alone for a nerve block is short and the postoperative analgesic effect is limited. Dexmedetomidine combined with ropivacaine can enhance peripheral nerve block and prolong sensory block time (45, 46). Our present study showed that ropivacaine plus dexmedetomidine (μg/kg−1) had better analgesic efficacy than ropivacaine alone. The postoperative pain score of the RD group was significantly lower than that of the R group in the resting and exercise state, similar to previous reports of erector spinae plane block, dexmedetomidine combined with ropivacaine reduced pain scores at 24 h after breast cancer surgery (18). Our rat model (41), which showed that the combination of dexmedetomidine and ropivacaine can increase the block time of the sensory drinking motor, and the block time is related to the concentration of the dexmedetomidine and ropivacaine. On the contrary, Abdallah et al. suggested that the addition of deep serratus anterior block to general analgesia cannot improve the quality of rehabilitation in patients undergoing outpatient breast cancer surgery (47), this may be related to the small number of cases enrolled and the selection of patients with larger weight (BMI < 35) undergoing ambulatory surgery. Patients with antepartum obesity may require decreased ropivacaine concentration for epidural labor analgesia when co-administered with 0.5 µg/ml dexmedetomidine (48). However, it was a very meaningful study, and more studies are needed to confirm the effect of serratus anterior block in breast cancer surgery.

Reducing perioperative opioid use is one of the current goals of enhanced recovery after surgery, which aims to reduce potential opioid-related side effects. Regional nerve block plays an important role in opioid reduction. In this study, dexmedetomidine combined with ropivacaine can reduce the postoperative dosage of sufentanil and improve patient satisfaction. Previous reports indicate that dexmedetomidine combined with a paravertebral block was found to reduce opioid dosage during thoracoscopic surgery (49). Paraspinal thoracic block can reduce the consumption of opioids in early postoperative breast surgery, which may be related to the anesthetic time of ropivacaine (50) avoided the complications of epidural block in breast surgery patients (51). Unilateral ESPB was administered during modified radical mastectomy, similar to a unilateral thoracic epidural block and without hemodynamic side effects, can reduce the use of opioids after breast cancer (52).

In conclusion, under the conditions of the present study, the ultrasound-guided deep serratus anterior plane block combined with dexmedetomidine plus ropivacaine may improve the QoR-15 with ropivacaine alone in patients undergoing modified radical mastectomy and indicate that it may be a useful intervention to aid recovery following breast cancer surgery. Furthermore, participants in the ropivacaine with DEX group met the superior pain relief in the early postoperative period, reduced the postoperative cumulative opioid consumption, and increased patient satisfaction, and there was no increase in the incidence of complications.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the ethics committee of Bethune International Peace Hospital. The patients/participants provided their written informed consent to participate in this study.

YW was involved in the conception and design of the study. YK collected the data. YL prepared the placebo tablets. BF analyzed the data. YW drafted the first and final version of the manuscript. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.