The effects of a modified deep serratus anterior plane block on surgical stress and perioperative neurocognitive disorders in elderly patients undergoing thoracic surgery: a randomized clinical study

Introduction

Perioperative neurocognitive disorder (PND), a generic term for pre- and postoperative cognitive impairment, usually refers to damage to memory, learning, attention, or psychomotor performance (1). In recent years, as the aging population has gradually increased, there has been a corresponding rise in the proportion of elderly individuals in the surgical population. However, the exact cause of cognitive decline after anesthesia and surgery remains unclear. The type and dosage of general anesthesia drugs, the surgical traumatic stress response, the inflammatory response, postoperative infection, and postoperative respiratory complications can contribute to early PND (2,3). Among these, the perioperative stress reaction is an important risk factor for PND in elderly patients (4). Based on the current basic and clinical research results, controlling or effectively reducing the stress response in elderly patients during the perioperative period could effectively reduce the occurrence of PND.

Minimally invasive approaches to lung resection, such as video-assisted thoracoscopic surgery and robotic-assisted thoracoscopic surgery, have been associated with lower rates of pulmonary complications and faster recovery compared with open thoracotomy. However, pain after minimally invasive thoracic surgery can still be severe. The pain syndrome after thoracic surgery is multifactorial, with components of inflammation from local tissue trauma, nociceptive somatic pain, visceral pain, neuropathic pain from nerve injury and irritation, and referred pain from diaphragmatic and mediastinal manipulation. Additionally, it provides strong stimulation, causing a stress response (5). Therefore, the incidence of PND in elderly patients undergoing thoracic surgery is higher than that in patients undergoing other surgeries (6). Thus, special attention should be paid to reducing the perioperative stress response in elderly patients undergoing thoracic surgery to reduce the incidence of PND.

The serratus anterior plane block (SAPB) is a novel chest wall nerve block technique. SAPB has a unique capability to infiltrate and effectively block the lateral cutaneous branches of the T2–T9 intercostal nerves, while also extending its reach to the long thoracic and thoracic dorsal nerves (7,8). Notably, SAPB achieves an analgesic effect that surpasses the capabilities of the thoracic paravertebral block (TPVB) and the intercostal nerve block (INB) (9).

When the SAPB is employed clinically, local anesthetics are injected when the needle tip reaches the surface of the serratus anterior muscle, which is called a superficial serratus anterior plane block (SSPB). When the puncture needle passes through the anterior serrate muscle and reaches the rib surface, a local anesthetic is injected, which is the deep serratus anterior plane block (DSPB). Research indicates that the SSPB has a block range spanning T2–T9, and an average duration of 12 h (700–780 min). Conversely, the DSPB has a relatively shorter duration and a narrower block range. Nevertheless, the DSPB typically has a block duration of 3.5–10 h, covering typical thoracic incision positions (the incision began 2 cm below the subscapular angle and extended along the 5^th or 6^th intercostal space to the anterior axillary line and back around the internal margin of the scapula to the paraspinous process) encountered in basic clinical practice (10). George et al. (11) described a morbidly obese patient who failed tracheal catheter extubation owing to acute pain after thoracotomy. After placing a deep serratus anterior plane catheter, adequate analgesia and successful extubation were achieved. Abdallah et al. (12) showed that DSPB and SSPB techniques were equally effective in early postoperative analgesia for breast cancer. Opioid consumption and resting pain scores during hospitalization are similar in patients using both nerve block methods. These results provide a theoretical and practical basis for employing the DSPB technique for chest analgesia (13).

Currently, detailed reports on the intra- and postoperative analgesic effects of DSPB in patients undergoing thoracic surgery are lacking. Moreover, the inhibitory effect of the DSPB on the stress response during surgery in elderly patients and its subsequent effects on PND remain unclear. This study aimed to assess the effects of a modified DSPB combined with general anesthesia on surgical stress, postoperative pain, and Montreal Cognitive Assessment (MoCA) scores related to PND in elderly patients undergoing thoracic surgery. This study aimed to offer novel insights into perioperative analgesia and strategies for the prevention and treatment of PND in elderly patients undergoing thoracic surgery. We present this article in accordance with the CONSORT reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/rc).

Methods

Study design

The study was approved by the Medical Ethics Committee of the Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University (No. KY-20230208–0019-01). In accordance with ethical guidelines, signed informed consent forms were obtained from the patients themselves or, when applicable, from family members. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Study population

To be eligible for inclusion in the study, the patients had to meet the following inclusion criteria: (I) be aged 65 to 80 years; (II) have an American Society of Anesthesiologists classification of I–II; (III) be scheduled for thoracic surgery. Patients were excluded from the study if they met any of the following exclusion criteria: (I) had a mini-mental state examination (MMSE) scale score ≤23 points; (II) had a neurological disease predisposing them to cognitive decline, such as Parkinson’s disease, vascular dementia, cerebral hemorrhage, brain tumor, or hepatic encephalopathy; (III) had a history of cognitive disorders, including cerebral hemorrhage, drug abuse, intracranial tumors, encephalitis, and brain trauma; (IV) were unable to complete the psychological tests due to visual impairment, hearing impairment, or physical dysfunction; (V) had a history of congenital intellectual disability or mental illness; (VI) had hyperalgesia or dysalgesia; (VII) had refractory cancer pain; and/or (VIII) were illiterate. In total, 66 patients who underwent thoracic surgery were observed from March 2023 to January 2024, and 60 patients who met the inclusion criteria were included in the final analysis.

Study protocol

Using a random number table, the 66 patients were randomly allocated to the DSPB group (n=33) and local group (n=33). Their cognitive function was assessed using the MoCA scale. All patients were instructed to avoid eating for 8 h and drinking for 4 h before surgery, and none of the patients took any preoperative medication.

The patients were monitored continuously using electrocardiogram, pulse oximetry, respiratory rate, mean arterial pressure (MAP), and bispectral index (BIS) values. After a period of pre-oxygenation, all the patients had general anesthesia induced with intravenous midazolam (0.05 mg/kg), propofol (2 mg/kg), sufentanil (0.6 µg/kg), and cisatracurium (0.2 mg/kg). All the patients were intubated with a Shiley endobronchial tube to achieve lung isolation, and fiberoptic bronchoscopy was used to confirm the correct positioning. The hemodynamic goal was to maintain the systolic blood pressure within 20% of the baseline.

Anesthesia maintenance comprised the continuous inhalation of sevoflurane (1–2%), continuous infusion of remifentanil (0.1–0.2 µg/kg·min), continuous infusion of propofol (4–6 mg/kg·h), and additional cis-atracurium as required. Throughout the operation, the BIS values were maintained between 40 and 60 mmHg, and end-tidal carbon dioxide pressure (P_ETCO₂) was maintained between 35 and 40 mmHg. Mechanical ventilation settings, the need for invasive hemodynamic monitoring, and central venous access were at the discretion of the treating anesthesiologist.

Envelopes were opened after the induction of general anesthesia to reveal the group allocation. The blocks were performed under fully aseptic conditions according to randomization before the commencement of the surgery. All the patients received 0.5% ropivacaine (20 mL), administered as part of the specified blocks.

The DSPB group underwent a modified DSPB after tracheal intubation, following the methods for unilateral DSPB under ultrasound guidance. The patient was placed in a lateral position, the midaxillary line of the patient’s surgical side was found, and a 7-gauge needle was inserted vertically at the 4^th or 5^th rib. After touching the rib, the needle was slightly pulled back, and 0.5% ropivacaine (20 mL) was injected. This method is easy to operate, does not require ultrasonic guidance, depends on instruments and equipment, and does not require high puncture skills. Conversely, the local group received a local infiltration of 0.5% ropivacaine (20 mL) at the surgical incision site, and the completion time of the block was recorded (Figure 1). Subsequently, the patient’s vital signs and P_ETCO₂ were recorded at the following five additional time points: after endotracheal intubation; at incision and endoscopy; 1 h after the block; at the end of surgery; and 30 min after surgery. Simultaneously, venous blood (4 mL) was collected at the following four time points: after endotracheal intubation (T0); at incision and endoscopy (T1); 1 h after the block (T2); and 30 min after surgery (T3). The serum, obtained through centrifugation, was stored at −80 ℃ for the subsequent determination of malondialdehyde (MDA), superoxide dismutase (SOD), and serum cortisol.

Figure 1 Schematic diagram of the block depth of SSPB and DSPB. On the left is SSPB and on the right is DSPB. Id is the latissimus dorsi muscle and Sa is the serratus anterior muscle. r5 is the fifth rib and r4 is the fourth rib. DSPB, deep serratus anterior plane block; SSPB, superficial serratus anterior plane block.

Additionally, 1 h post-operation, arterial blood (1 mL) was collected for the blood gas analysis to determine the relevant indices. After surgery, the patients were provided with a self-controlled analgesia pump (100 ug of sufentanil, 100 ug of dexmedetomidine, and 4 mg of tropisetron) with a continuous infusion rate of 2 mL/h, a patient-controlled dose of 2 mL/h, and a locking time of 30 min.

Postoperative pain was evaluated using the visual analog scale (VAS) at extubation and 30 min after extubation, 2 h after extubation, and 6 h after extubation. Drug use was recorded before and after extubation. On the seventh day after surgery or the day of discharge, the cognitive function of the patients was re-assessed using the MoCA scale.

Statistical analysis

The statistical software SPSS (version 26.0) and GraphPad Prism (version 8.0) were used for the statistical analysis Sex, surgical method, education level, and drug use during the extubation period were analyzed using the Chi-squared test. Age, length of hospital stay, and intraoperative blood gas indicators were analyzed using the independent sample t-test. For measures involving repeated observations, the generalized estimation equation was employed to compare the statistical differences between the groups at different time points. Statistical significance was set at P<0.05. The main index of this study was the VAS score between the two groups of patients. According to the pretest results, in the DSPB group, the mean VAS pain score at rest was 4.5 [standard deviation (SD) =1.9]. While in the local group, the mean VAS pain score at rest was 6.1 (SD =1.6), with bilateral α=0.05 and β=0.2. A formula (n=(〖(Z_α+Z_β)〗^2 (1+1⁄k)σ^2)/δ^2, k=1) was used to calculate n=30. By calculating the percentage of lost visits at 10%, it was determined that 33 patients were required for each group.

Results

Disposition and baseline characteristics of patients

Between March 2023 and January 2024, 66 patients aged 65–80 years were enrolled in the study. Of these patients, six were excluded from the study; three were lost to follow-up (n=3), two experienced adverse reactions (n=2), and one exited the study (n=1). The DSPB group comprised 30 patients and the local group comprised 30 patients. The patients underwent standardized anesthetic and surgical procedures and completed all the evaluation assessments. Finally, we performed a statistical analysis of the patients’ data and created a flow diagram for the trial (Figure 2).

Figure 2 Flow chart. DSPB, deep serratus anterior plane block.

There were no statistically significant differences between the two groups in terms of sex, age, type of surgery, and educational level (Table 1).

Comparison of VAS score, drug use, stress indices, MAP, HR, oxygen saturation (SpO₂), P_ETCO₂, BIS, and MoCA

The VAS score of the DSPB group was significantly lower than that of the local group at each time point (P<0.05) (Figure 3A). There were no significant differences between the two groups in terms of drug use during tracheal extubation (Table 2). Additionally, there were no significant differences in the MoCA scale score between the two groups (Figure 3B).

Figure 3 Chart of VAS, MoCA, stress indexes, including MDA, SOD, serum cortisol, and hospital stay. (A) Drug use during the extubation period. T0 (extubation); T1 (30 min after extubation); T2 (1 h after extubation); T3 (6 h after extubation); (B) MoCA scale. There was no statistically significant difference in the MoCA scale scores between the local group (black) and DSPB group (gray) at any time point. T0 (preoperative); T1 (at discharge or 7 days after surgery); (C) the stress indexes included MDA, SOD, and cortisol. There was no statistically significant difference in the serum MDA stress indices between the local group (black) and DSPB group (gray) at each time point. T0 (after tracheal intubation); T1 (when the thoracoscope accessed the incision; T2 (1 h after nerve block); T3 (30 min after surgery); (D) there was no statistically significant difference in the serum SOD stress indices between the local group (black) and DSPB group (gray) at each time point. T0 (after tracheal intubation); T1 (when the thoracoscope accessed the incision); T2 (1 h after nerve block); T3 (30 min after surgery); (E) there was no statistically significant difference in the serum cortisol levels between the local group (black) and DSPB group (gray) at any time point. T0 (after tracheal intubation); T1 (when the thoracoscope accessed the incision); T2 (1 h after nerve block); T3 (30 min after surgery); (F) hospital stays. There was a statistically significant difference in the length of hospital stay between two groups; the length of hospital stay was shorter in the DSPB group (gray) than in the local group (black). *, P<0.05; ns, not significant. DSPB, deep serratus anterior plane block; MDA, malondialdehyde; MoCA, Montreal Cognitive Assessment; SOD, superoxide dismutase; VAS, visual analog scale.

The stress indices, such as MDA, SOD, and cortisol, were detected in the serum of the patients (P>0.05) (Figure 3C-3E). There were no significant differences between the two groups in terms of MAP (P=0.22), heart rate (HR) (P=0.40), peripheral capillary SpO₂ (P=0.20), P_ETCO₂ (P=0.94), or the BIS (P=0.51) (Table 3). There were no significant differences in the intraoperative blood gas analysis results between the two groups, except in relation to total carbon dioxide (TCO₂) (P<0.05) (Table 4). The length of hospital stay was shorter in the DSPB group than the local group (Figure 3F).

Discussion

This novel clinical trial examined the use of a modified DSPB under general anesthesia to determine whether it could reduce surgical stress and prevent perioperative neurocognitive impairment. Dr. Rafael Blanco first described SAPB in 2013, when he observed local anesthetic penetration at the midaxillary line in the superficial or deep interfascial plane of the serratus anterior muscle (14). Mayes et al. performed diffusion tests with methylene blue solution on cadaver specimens and showed that the extension area included the lateral cutaneous branches of the second to sixth intercostal nerves, long thoracic nerve, and thoracodorsal nerve in the anterior serratus space (15). Anatomically, SAPB not only blocks the intercostal nerve by infiltrating the lateral cutaneous branch of the intercostal nerve, but also infiltrates the long thoracic nerve and thoracodorsal nerve, providing more comprehensive analgesia in the anterolateral chest wall than thoracic epidural block (TEB), TPVB, and INB (16,17). In this clinical trial, we assessed the postoperative pain scores (VAS scores) of the patients in the two groups (i.e., the DSPB group and the local group). The DSPB group had lower scores than the local group, indicating that the modified deep serratus anterior muscle had a more effective analgesic effect.

Neuroendocrine changes induced by surgical stress mainly affect the hypothalamic-pituitary-adrenal and sympathetic adrenal medulla axes. Surgery and anesthesia are the main stressors affecting patients’ perioperative stress responses (18). Currently, double-lumen endotracheal tubes are commonly used in thoracic surgery for lung isolation under general anesthesia. However, general anesthesia alone may not completely block the increased secretion of the pituitary gland and adrenal medulla caused by stimulation, such as intubation and surgery. Surgical stimulation can increase the concentration of catecholamines and cortisol in patients’ blood, resulting in hemodynamic changes, such as increased blood pressure and HR. Propofol has been shown to have a limited effect in attenuating hypothalamic axis activation in thoracic surgery, and remifentanil is often used to control the stress responses, which are generally negligible in this context (19). Many studies have shown that combined anesthesia to block incision pain can reduce stress responses, such as cardiovascular responses. This reduction can help avoid the prolonged recovery period caused by the addition of anesthetic drugs to maintain stable hemodynamics (20,21). As a nerve block method commonly used in thoracic surgery, the DSPB can block pain signal transmission from the thoracic incision to the spinal cord, thereby reducing perioperative stress reactions and cardiovascular adverse reactions, and relieving postoperative incision pain in patients undergoing thoracic surgery. In this trial, no significant differences were observed in MDA, SOD, and cortisol between the groups. However, a study has reported oxidative stress damage in the hippocampi of PND mice, manifesting as decreased SOD activity and increased reactive oxygen species (ROS) and MDA expression in the hippocampus (22). We also compared the MAP, HR, and SpO₂ between the two groups at each time point, but the differences were not statistically significant. Thus, the hemodynamics in both groups were relatively stable.

Elevated glucocorticoid levels induced by stress can increase blood glucose levels. Therefore, we compared the blood gas indices between the two groups during surgery to examine their effects. The results revealed a significant difference in relation to TCO₂ only (P<0.05), such that the DSPB group had lower TCO₂ levels than the local group. This suggests that the modified DSPB may not only enhance local analgesia but may also improve the ventilation-to-blood flow ratio in the blocked lung during one-lung ventilation, potentially preventing the accumulation of carbon dioxide in the body to a certain extent. Thus, the modified DSPB may play a role in regulating the autonomic nervous system. The results revealed no significant differences in the blood glucose levels between the two groups. Jung et al. suggested that a high propofol infusion rate for deep anesthesia in pulmonary surgery can reduce the perioperative glucose response more effectively than shallow anesthesia, but does not affect the immediate postoperative blood glucose results (23). An extended follow-up time may be required to explore the effect of the modified DSPB on glucose and its clinical significance further. Therefore, further investigation is warranted to assess the effect of the modified DSPB on stress control during thoracic surgery.

The surgical stress response is recognized as a risk factor for PND, especially in the elderly surgical population. A study has confirmed that nearly 10% of elderly people have objective cognitive impairment three months after noncardiac surgery (as determined by a series of neuropsychological tests) (24). In this trial, we used the MoCA scale to assess the cognitive function of patients scheduled for elective thoracic surgery the day before the operation. The sensitivity of the MoCA scale to mild cognitive dysfunction is higher than that of the MMSE scale, especially in elderly patients; however, the MoCA scale also has certain limitations, including factors such as the education level and age of patients (25,26). In this trial, the elderly patients, who were all aged over 65 years, and most of whom were educated to the junior high school level, were followed up until the seventh day after surgery or the day of discharge (within 7 days of hospitalization). Their cognitive function was re-assessed using the MoCA scale. The results revealed no statistically significant difference in the MoCA scores between the two groups. Notably, patients in the modified DSPB group had shorter hospital stays. However, the MoCA scores of both groups were higher after surgery than preoperatively. This could be because the time between the two assessments was too short, and the patients were familiar with the scale process and content. Due to the limitations of our research conditions, our study was confined to the hospitalization period of patients, and the scope of the MoCA score assessment was limited.

This study introduced an innovative technique for completing a modified DSPB without ultrasound guidance. This technique relies primarily on the anatomical structure of the serratus anterior muscle, and specifically targets the deep plane between the serratus anterior muscle, external intercostal muscle, and ribs. It does not require ultrasound equipment, making it a simpler and more easily operable procedure that is particularly suitable for widespread implementation in small hospitals. In our preliminary experiments, we observed that the blocking range and ultrasound images of the modified DSPB were comparable to those of the traditional DSPB, and no adverse reactions have been observed thus far. Compared to local infiltration, modified DSPB has advantages such as superior analgesia, lower postoperative pain scores, and shorter hospital stays.

This study had several limitations, including a small sample size, the absence of a double-blind method, a relatively short follow-up period, a lack of a comprehensive neuropsychological evaluation system to assess cognitive function comprehensively, and no record of postoperative analgesic pump drug consumption. To address these limitations, future studies should seek to expand the sample size, extend the follow-up period, and enhance the evaluation methods for PND. Future research should also focus on investigating the effects of the modified DSPB on surgical stress and PND in elderly patients undergoing thoracic surgery.

Conclusions

Compared to local infiltration, the modified DSPB in elderly patients undergoing thoracic surgery had a superior analgesic efficacy, as evidenced by lower VAS scores, and led to shorter hospital stays. However, no significant differences were observed in the perioperative stress levels or MoCA scores related to PND.

Acknowledgments

The authors would like to thank the Hangzhou First People’s Hospital for providing a platform for clinical trials. We would also like to thank all the medical staff at the Department of Anesthesiology of Hangzhou First People’s Hospital for their help and guidance.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/rc

Trial Protocol: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/tp

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/prf

Funding: This work was supported by the Medical Science and Technology Project of Zhejiang Province (No. 2021KY872), the Medical and Health Research Project of Zhejiang Province (No. 2025KY1050), and the Construction Fund of Key Medical Disciplines of Hangzhou (Anesthesia and Pain Medicine OO20200484).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-726/coif). M.G. received payment for lectures by Medtronic, Ethicon and MSD. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Medical Ethics Committee of the Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University (No. KY-20230208–0019-01). In accordance with ethical guidelines, signed informed consent forms were obtained from the patients themselves or, when applicable, from family members. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)