The perioperative stress response is associated with immunosuppression [17], and several studies have suggested a connection between inflammatory responses and tumor development [18–20]. Therefore, there is a critical need for the development of optimal methods to reduce perioperative stress and inflammatory responses in cancer patients. The modified PNB is a new technique for providing effective perioperative anesthesia and analgesia in patients undergoing breast surgery [21]. It has been shown to provide adequate perioperative pain relief, which is essential for the reduction of stress and inflammatory responses [17]. The SGB has a large range of clinical indications, including vasomotor syndromes, and both sympathetic-maintained and neuropathic pain syndromes [22–24]. Nevertheless, while the individual effects of PNB and SGB have been previously evaluated, few studies have investigated the effectiveness of a combined PNB and SGB. Therefore, this study aimed to determine whether the combination of an ultrasound-guided SGB and a modified PNB is more effective than a PNB alone in reducing stress and inflammatory responses in women undergoing modified radical mastectomy.
The results of this study indicated that the plasma levels of cortisol and glucose during surgery were blunted with the combined SGB and PNB approach. The combined block method also resulted in significantly lower postoperative IL-6 and TNF-a levels compared to the control group; additional advantages included a more stable perioperative HR, more effective relief of acute pain up to 12 hours postoperatively, and better postoperative sleep quality. No serious side effects were detected in either group. Thus, the combined SGB and PNB approach can be successfully used in conjunction with general anesthesia to suppress stress and inflammatory responses in patients undergoing modified radical mastectomy.
It is well known that changes in neuroendocrine mediators and cytokines through the direct activation of the somatic and sympathetic nervous systems can accurately reflect the perioperative stress response. Cortisol is the major glucocorticoid secreted by the zona fasciculata and zona reticularis [25]. The plasma levels of cortisol and glucose are sensitive indicators of the stress response, and accurately reflect the stimulus intensity [26, 27]. In our study, cortisol levels were significantly lower at the end of the surgery, while glucose levels were significantly lower immediately after incision in the SGB group compared to the control group. Our findings are consistent with those of Chen et al. [28], who reported that SGB reduced stress responses in patients undergoing elective laparoscopic cholecystectomy. In addition, surgical trauma is also likely to enhance a patient’s inflammatory response [29], due to the increased incidence of postoperative complications.
IL-6 is highly expressed during inflammatory responses to conditions of stress, and can be used to assess the severity of surgical trauma [30]. The observation of a reduction in IL-6 levels in the SGB group suggests that the combined block approach can attenuate the inflammatory response. This result is supported by a study conducted by Zhu et al. [31], who reported on the ability of the SGB to reduce the inflammatory response in patients undergoing laparoscopic colorectal cancer surgery. TNF-a is one of the most important mediators of systemic inflammation, and is released within a few minutes after local or systemic tissue injury [32]. Therefore, it can be used as an indicator of an early inflammatory reaction [32]. In our trial, the plasma levels of TNF-a were significantly lower in the SGB group at 24 hours postoperatively; this may reflect the alleviation of the inflammatory response by SGB. IL-8 plays an important role in acute inflammation [33]. While there was no significant difference in plasma IL-8 values between the SGB and control groups, we observed a significant reduction of IL-8 from T0 to T1 in both groups. We speculate that this reduction may have been related to preoperative anxiety; however, previous studies have suggested that anxiety may not be significantly associated with inflammatory markers such as IL-8 [34, 35]. Therefore, further research is needed to elucidate the relationship between preoperative anxiety and changes in inflammatory markers.
Previous clinical trials have reported that SGB can provide effective analgesia [14, 36]. Our results further confirmed the effectiveness of SGB, as we documented effective analgesia for up to 12 hours. As postoperative analgesia reduces the stress response, the analgesic effect of SGB may partly explain the reduction of cortisol, glucose, and inflammatory factor levels in the present study. Patients in the SGB group also exhibited significantly more stable HR changes compared to the control group; similar results were also reported by Chen et al. [28] In the present study, we also found that postoperative sleep quality was significantly higher in the SGB group; this supports the use of the combined block approach in patients with perioperative sleep disorders.
Limitations
This study was limited by its relatively small sample size, and its inclusion of patients with a specific medical condition. Therefore, the external generalizability of our findings may be limited. Also, the use of sufentanil for analgesia during surgery may have affected our results, due to its intrinsic ability to influence the neuroimmunoendocrine network. Furthermore, we did not assess long-term clinical effects of combined PNB and SGB such as patient prognosis, cancer migration, interference with the immune system, and complications. Therefore, our results are preliminary, and further studies are required to evaluate long-term outcomes after the combined use of the SGB and PNB.