Evaluating Modified Ultrasound-Guided Serratus Anterior Plane Block for Enhanced Postoperative Recovery in Thoracoscopic Lobectomy Patients

Background

Lung cancer is the leading cause of cancer-related mortality worldwide [1,2]. Surgical resection of early-stage non-small-cell lung cancer offers the best chance of a cure [3]. Compared with open thoracotomy, thoracoscopic lobectomy is less invasive, involves smaller skin incisions, and is associated with quicker recovery, more precision, and better outcomes [4]. However, minimally invasive thoracic surgery still causes moderate to severe postoperative pain [5]. Poorly controlled early postoperative pain increases the risk of postoperative pulmonary complications (PPCs) that can dampen effective cough and expectoration, impair the quality of recovery, and are potential risk factors for subsequent CPSP [11]. Therefore, pain management, as an integral part and cornerstone of Enhanced Recovery after Surgery (ERAS), plays an important role [12]. However, compliance with pain management protocols for ERAS remains poor and ambiguous [13].

Perioperative pain management in chest surgeries is challenging. Previous studies were too heterogenous to determine a criterion standard for analgesia in thoracoscopic surgery [14,15]. Recently, the concept of opioid-sparing analgesics has been popularized owing to the serious adverse effects of opioids, including addiction and respiratory depression [16]. Currently, regional analgesia has become popular in thoracic surgery [17,18]. Although regional analgesia techniques such as thoracic epidural analgesia (TEA) and paravertebral analgesia (PVA) provide optimal pain relief, they are technically difficult to perform and can also result in some complications, ranging from total spinal anesthesia and inadvertent intravascular injection to pneumothorax [19,20].

Presently, ultrasound-guided interfascial blocks, such as ultrasound-guided serratus anterior plane block (SAPB), are used in thoracoscopic surgery. SAPB is a relatively novel analgesic technique proposed by Blanco; it aims to deposit a local anesthetic in the interfascial plane through which peripheral nerves pass to alleviate perioperative pain [21,22]. Both superficial and deep SAPB can alleviate pain following modified radical mastectomy; however limited evidence indicates that deep SAPB relieves pain to a greater degree than superficial SAPB [23–26]. It is difficult to quickly distinguish the 2 interfascial planes in clinical practice even with the assistance of ultrasound guidance. In such cases, intramuscular injections are inevitable, thus limiting the diffusion of local anesthetics and reducing the analgesic effects of SAPB [27]. Furthermore, it can injure the blood vessels and pleura when puncturing the intercostal space. Therefore, the present article introduces a modified ultrasound-guided serratus anterior plane block (MUG-SAPB), which anchors the rib, but not the intercostal space, for local anesthetic injection in patients scheduled for thoracoscopic lobectomy, and evaluated its effectiveness in mitigating need for postoperative analgesia.

Material and Methods

STUDY DESIGN AND PATIENT POPULATION:

This prospective, randomized, single-center study was conducted at the General Hospital of Western Theater Command and was approved by the institutional review board of the hospital. The study was conducted from July 2022 to February 2023 and was registered with the Chinese Clinical Trial Registry (ChiCTR2300067338). Patients who met the eligibility criteria were invited to participate in this study, and written informed consent was obtained from all enrolled patients. Overall, 86 patients were recruited and 8 of them were excluded. The remaining 78 patients were randomly allocated to receive either MUG-SAPB with patient-controlled intravenous analgesia (PCIA) or PCIA alone. Four patients were switched to thoracotomy, 1 patient required postoperative intubation, 1 patient needed rescue analgesia with nerve block, and these patients were also excluded (Figure 1). Ultimately, 72 patients were included in the final analysis.

The inclusion criteria were the following: American Society of Anesthesiologists (ASA) physical status classification I–III; age, 18–70 years; and scheduled for elective thoracoscopic lobectomy. The exclusion criteria were the following: refuse to participate; contraindications to regional anesthesia, ropivacaine, or dexamethasone; switching to open thoracotomy during surgery; history of pre-existing chronic pain; postoperative reintubation; opiate abuse history; and cognitive dysfunction, which could interfere with accurate assessments of analgesia and postoperative quality recovery.

The patients were allocated to the 2 groups using a computer-generated random number table. With the Java generates 1–100 random numbers, patients who were allocated even numbers were assigned to the MUG-SAPB group, and those who were allocated odd numbers were assigned to the PCIA group. Although patients were not aware of the grouping beforehand, and MUG-SAPB is performed following anesthesia, the traces left by the MUG-SAPB operation cannot fully guarantee that the patient is blind to the grouping, which is determined by the nature of the study. However, the follow-up personnel, caregivers, and statisticians did not know the intervention group to ensure that the results were unbiased.

MUG-SAPB PROCEDURES:

Before the commencement of surgery, nerve blocks in the UMG-SAPB group were administered under aseptic conditions by consultant anesthesiologists with extensive experience in regional anesthesia, for these who obtained the title of attending physician, and had used ultrasound-guided nerve block for over 2 years. MUG-SAPB was performed using a 22-gauge echogenic needle (Stimuplex®D, Braun, 80 mm), an ultrasound machine (SonoSite, USA), and a linear ultrasound transducer covered in sterile film preoperatively. Patients were placed in the supine position with the arm abducted to 90°, and the skin was prepared using iodophor. The block method and the patient position are referred to as the Blanco method and the Buggy position, respectively [21,28]. The most characteristic difference of this method in comparison with previous methods of SAPB is that we did not distinguish between the superficial or deep interfascial planes of the serratus anterior muscle; rather, local anesthetics were injected directly using the rib as the anatomical landmark. The ultrasonography probe was first placed in the sagittal plane over the midline of the clavicle. The first bone identified under the clavicle was the second rib. The probe was moved caudally to identify the fifth rib and moved laterally and caudally to identify its mid-axillary region along with the thoracic cage (Video 1). The needle was inserted using an in-plane technique to penetrate the serratus anterior muscle, and ropivacaine plus dexamethasone mix (40 mL) was injected under continuous ultrasound guidance over the surface of the fifth rib (Figure 2A; Video 2). Spindle diffusion of the local anesthetic deep into the serratus anterior muscle was observed under ultrasound guidance (Figure 2B). The anesthesiologist who performed MUG-SAPB did not participate in further data collection and analysis.

ANESTHESIA AND SURGERY:

General anesthesia with intubation was administered to patients who were scheduled for thoracoscopic lobectomy. All patients in this trail were intubated using a full-view double-lumen endotracheal tube (VDLT) to achieve lung isolation and confirm correct positioning with a real-time monitor. For women, a 32-Fr VDLT was chosen, while for men, a 35-Fr was chosen. Sufentanil, a highly selective μ receptor agonist with rapid onset and powerful analgesic effect, was used for the induction of anesthesia [29]. As needed, sufentanil was added at the beginning of the surgery to alleviate strong irritation. A sevoflurane/oxygen/air mix, remifentanil, and dexmedetomidine were used to maintain the depth of anesthesia, with the bispectral index (BIS) fluctuating from 40 to 65. Rocuronium was administrated intermittently (every half hour) to sustain muscle relaxation. Postoperatively, the VDLT was removed uniformly and PCIA was performed unless contraindicated. Multimodal analgesia was employed to alleviate pain and enhance recovery after surgery. The analgesic formula included 150 mL normal saline with 30 mg oxycodone, 250 mg flurbiprofen axetil, and 10 mg tropisetron, a classic formula of opioid and NSAID. These drugs were administered at a loading dose of 2 mL, a maintenance dose of 2.5 mL/h, and a patient-controlled analgesia (PCA) dose of 2 mL. The lock time interval between each PCA was 0.5 h, and the maximum analgesics administered per hour was 12 mL. Considering the analgesic capping effect of NSAID and their potential adverse effects, when patients needed pain relief beyond PCIA, we added butorphanol for rescue analgesia.

The thoracoscopic lobectomy approach used in our hospital is a three-part technique that incorporates two 1-cm and one 4-cm utility incisions. If thoracoscopy was not feasible due to excessive bleeding or difficulty in removing the tumor, open thoracotomy was performed. Considering the greater trauma associated with open thoracotomy than with thoracoscopy, we excluded patients who underwent open thoracotomy when analyzing the results. Postoperatively, the VDLTs were removed, the patients were transferred to the PACU, and then to the ward once they met the PACU discharge criteria.

POSTOPERATIVE DATA COLLECTION:

In this trail, the visual analog scale (VAS) score (range 0–10; 0, no pain; 10, worst pain ever) at rest and during movements was used to assess the pain level. The VAS score during movement was assessed when the patients sat up, rolled over, or engaged in out-of-bed activities. Patients were interviewed postoperatively at 4, 8, 12, 20, 24, 48, and 72 h. Preoperative pain levels were also recorded to provide accurate pain management. Once the rest VAS score was >3 points, rescue analgesia was performed using intravenous butorphanol in a single dose of 0.5–1 mg. The times of rescue analgesia and frequency of PCA within 24 h were recorded. To evaluate recovery quality, the first ambulation (time since leaving the PACU) was noted. Here, we introduced a comfort score inspired by quality of recovery system (QoR-40) [30]. Good analgesia with fewer adverse effects is a delicate balance, and sufficient PCIA often accompanies with adverse effects of drugs. Comfort score within 24 h was used to assess patient satisfaction, especially regarding postoperative analgesia-related adverse effects. It consisted of 3 questions: including nausea or vomiting, dizziness, and drowsiness. For each question, the patients choose a score between 0 and 2. A score of 0 indicated dissatisfaction, while 2 indicated the highest satisfaction. Additionally, we recorded postoperative complications that occurred within the first 72 h. The incidence of hypoxemia (defined as the occurrence of SpO2<90% under air intake conditions), pneumonia (medical record query), mechanical ventilation, and other complications were also recorded by visiting the patients every day and using the hospital’s electronic patient record database.

STATISTICAL ANALYSIS:

Data were analyzed with GraphPad Prism 8.2.1 and IBM SPSS Statistic version 26. The primary outcome was the VAS score at 4, 8, 12, 20, 24, 48, and 72 h postoperatively. We calculated samples based on a comparison of means using PASS v15. The sample size was calculated for a significance level of 0.05 and power of 90%, with a standard deviation (SD) of 0.8 in the PCIA group and 1.4 in the UMG-SAPB group at 8 h postoperatively, which were derived from our preliminary study. A difference of 1.5 between the mean VAS scores was considered clinically significant. Consequently, 35 patients were required for each group.

Data were tested for distribution using the Kolmogorov-Smirnov test. Continuous and quantitative variables are expressed as mean and standard deviation (SD) when normally distributed and as median and interquartile ranges when non-normally distributed. Categorical variables are expressed as absolute and relative frequencies. Normally distributed data were compared using the unpaired t test and for non-normally distributed data, the Mann-Whitney U test or Wilcoxon rank sum test was used. A repeated-measures ANOVA was employed with group allocation and time as independent variables. The chi-square test or Fisher’s exact test was used for categorical data. When comparing multiple times, the Benjamin-Hochberg method was used for multiple comparison correction to reduce multiple comparisons problems. Statistical significance was set at P<0.05.

Results

The Consolidated Standards of Reporting Trials (CONSORT) flow diagram for this study is shown in Figure 1. Overall, 86 patients were initially enrolled, and 78 who satisfied the inclusion criteria were randomly assigned to receive either MUG-SAPB with PCIA or PCIA alone. In the final analysis, 6 patients were excluded; the procedure in 4 patients was switched to open thoracotomy intraoperatively; 1 patient required reintubation; and 1 patient required an extra nerve block for pain postoperatively. The 2 groups were comparable in terms of age, sex distribution, height, weight, body mass index (BMI), ASA physical status, and surgery duration (Table 1). Most patients in the 2 groups underwent lobectomy, with wedge resection performed in 7 and 9 patients in the groups respectively, when histopathological examination revealed benign lesions. The primary outcome, the VAS score at rest and during movement within 72 h postoperatively, is illustrated in Figure 3. The MUG-SAPB group revealed lower resting VAS scores at 4, 8, 12, 20, and 24 h postoperatively (P<0.01, P=0.03, P<0.01, P=0.03, and P=0.04, respectively) and lower movement VAS scores at 4, 8, and 12 h postoperatively (P=0.01, P=0.04, and P=0.04, respectively). The secondary outcomes are illustrated in Table 2. The mean sufentanil consumption intraoperatively was 32.2 μg in the MUG-SAPB group and 43.6 μg in the PCIA group (P=0.02). The mean remifentanil consumption intraoperatively was 1071.5 μg in the MUG-SAPB group and 1221.4 μg in the PCIA group (P=0.11). The numbers of rescue analgesics administered within 24 h were 2 and 9 in each group (P=0.04), and the frequencies of PCA administrated within 24 h were 10 and 19, respectively (P=0.03). The mean time to first postoperative ambulation was 5.8 h in the MUG-SAPB group and 7.4 h in the PCIA group (P=0.04). The comfort score was higher in the MUG-SAPB group than that in the PCIA group (5.1 vs 3.1, respectively, P=0.03). The overall incidence of postoperative complications, such as hypoxemia, pneumonia, bleeding, mechanical ventilation, arrhythmia, and infections, within 72 h was low, with similar rates observed between the groups (Table 3).

Discussion

We introduced the MUG-SAPB method and demonstrated its reliability in this randomized study. There was a significant improvement in pain relief and quality of recovery following thoracoscopic lobectomy in patients who underwent MUG-SAPB with PCIA compared with those who underwent PCIA alone. Furthermore, the MUG-SAPB group had less intraoperative opioid consumption, less postoperative rescue analgesia, and better recovery experience and quality.

SAPB can block the cutaneous branches of the intercostal nerve to provide analgesia between the T2 and T9 levels [31]. In the classic ultrasound-guided SAPB, precise identification of the superficial or deep fascial interspace of the serratus anterior muscle between the latissimus dorsi and serratus anterior muscle, or the serratus anterior and intercostal muscles, is possible [21,32]. Accurate injection into the fascial interspace is necessary for ideal diffusion of the local anesthetic and to ascertain the extent of the nerve block. However, it is difficult for junior anesthesiologists to quickly identify the interfascial plane using ultrasound and accurately inject local anesthetics in the fascial interspace, especially in some patients with high BMI or advanced age. Intramuscular injections, which may be difficult to avoid, diminish the analgesic efficacy of SAPB [27]. This may explain the large discrepancy in block duration and even lead to failure in clinical practice.

In this study, we modified the traditional ultrasound-guided SAPB technique. In contrast to the conventional SAPB procedure, it is not necessary to distinguish between the interfascial planes of the serratus anterior in our technique. We reduced the difficulty of manipulation by quickly identifying the fifth rib, piercing the serratus anterior muscle, and injecting the local anesthetic into the rib’s surface. Based on clinical experience, we speculate that this modified method is convenient to perform and quick for anesthesiologists to master. No complications related to the nerve block were observed in the MUG-SAPB group.

To assess the efficacy of the MUG-SAPB intervention, we separately evaluated and recorded the VAS scores at rest and during movement. Although the VAS score in response to pain intensity is important, it may not be accepted by patients as an indicator of a better recovery experience when accompanied by other debilitating adverse effects. Therefore, we introduced a comfort score that reflects the adverse effects associated with analgesia. The comfort score mainly consists of 3 questions: nausea or vomiting, dizziness, and drowsiness. The results revealed that MUG-SAPB with PCIA could significantly reduce postoperative pain at rest within 24 h and during movement within 12 h compared with PCIA alone. This difference in postoperative rest and movement VAS scores may have resulted from the higher requirements for analgesia during movements. According to our clinical observations, the pain on the first day following thoracoscopic lobectomy was the most severe and intolerable. The relatively short duration of action of regional anesthesia limits the utility of single-injection local anesthetics in patients who require prolonged pain relief. According to previous reports, duration of the sensory blockade produced by deep SAPB is approximately 440 min [21,33,34]. However, this duration may be insufficient for patients undergoing thoracoscopic lobectomy. Therefore, it is necessary to prolong the duration of action of local anesthetics for postoperative analgesia. Adjuvants, such as α2 agonist, opioids, and dexamethasone, have been tried for their ability to prolong the duration of analgesia in nerve blocks [35,36]. Several studies have suggested that adding perineural dexamethasone to local anesthetics when performing nerve blocks likely prolongs the analgesic duration by approximately 6–8 h [37–39]. Therefore, we added 8 mg dexamethasone to the local anesthetic in this single-injection nerve block. To reduce postoperative disturbances to patients, we did not continuously monitor the specific time of regional anesthesia. Although there is little evidence, the results of VAS score at rest 24 h postoperatively revealed an ideal analgesic effect in this trial. This possible “prolonged analgesia duration” in our study may be due to a lower pain threshold secondary to combined regional anesthesia and PCIA.

Moreover, MUG-SAPB significantly reduced the numbers of rescue analgesia administrations and frequency of PCA on the first postoperative day. Notably, the postoperative threshold for an analgesic intervention by anesthesiologists was a VAS score >3. A striking difference between this work and previous studies is that we calculated the frequency of rescue analgesia and PCA rather than the consumption of opioids. On the one hand, these parameters through the electronically programmable pump were precise and easy to access; on the other hand, considering individual differences, patients may have varying sensitivity to pain and unequal needs for opioids. Considering the timeliness of regional anesthesia, we only analyzed the frequency of rescue analgesia and PCA at the most painful time on the first day.

Another finding of this study was that the MUG-SAPB significantly reduced the intraoperative use of sufentanil. Pain stimulus is intense during the placement of the thoracoscopic incision, and the blood pressure and heart rate rise; subsequently, the blood pressure drops when the procedure is finished, thus resulting in blood pressure fluctuations during chest opening. However, we rarely required sufentanil for pain and reduced blood pressure fluctuations in the MUG-SAPB group, which may be due to the blockade of sensory nerves in the chest. We did not observe a significant difference in the use of remifentanil between the 2 groups because of the limited surgery time and continuous intraoperative fixed-dose pumping. Cumulative opioid doses or rescue analgesia can trigger opioid-related adverse effects, such as dizziness, drowsiness, nausea, vomiting, and urinary retention. This may also be one of the reasons why higher comfort scores were observed in the MUG-SAPB group, in which opioids were used less.

Poorly controlled postoperative pain is also associated with postoperative pulmonary complications, which in turn increase the time to mobilization and length of hospital stay [40]. Regional anesthesia is an effective method of postoperative analgesia following thoracic surgery [18]. As expected, patients ambulated earlier in the MUG-SAPB group. The mean time to first ambulation in the MUG-SAPB group was 1.6 h shorter than that in the PCIA group. Although the time difference does not appear large, it was at the expense of tolerating more severe pain to early ambulation in the PCIA group, which was verified by the movement VAS score (Figure 3). Previous studies lacked clear data on the relationship between SAPB and first ambulation. Early mobilization or active exercise may reduce the incidence of postoperative complications, although this phenomenon was not observed in our study. The overall incidence of postoperative complications such as hypoxemia, pneumonia, bleeding, mechanical ventilation, arrhythmia, and infections within 72 h was low, with similar rates observed between the groups. The lack a significant difference can be partially explained by the limited-inclusion population and by the short observation period of 72 h postoperatively.

Postoperative pain management is suitable not only for acute pain relief but also for decreasing the risk of CPSP; the incidence of CPSP is as high as 35.3% in thoracoscopic surgery [41]. Since CPSP is accompanied by long-lasting opioid use, unnecessary sufferings, and poor quality of life, reducing the risk factors of CPSP following thoracoscopic surgery will help patients avoid these issues [6]. However, we did not track the incidence of CPSP in this study, which focused only on short-term pain due to a limited observation period. Currently, the relationship between regional anesthesia and the incidence of CPSP was is unclear and merits comprehensive discussion [42,43], which is worthy of further clinical research to provide more compelling evidence.

This study had some limitations. MUG-SAPB was performed when the patients were already anesthetized, and it was impossible to calculate the specific pain-loss area following regional anesthesia. Therefore, we did not perform a formal dermatomal assessment of the block, which raises the possibility of block failure. However, our rationale was that performing this modified interfascial block technique following general anesthesia is consistent with routine clinical practice; therefore, our results should be relevant to practice elsewhere. The slow onset of the interfascial block was not optimal for accurate measurements. Additionally, clinicians were not blinded to the intervention due to the study design. Finally, besides the exclusion criteria in the registration form, we have added several exclusion criteria based on the actual situation of the study, which may have contributed to selection bias.

Conclusions

We demonstrated that MUG-SAPB with PCIA can effectively relieve postoperative pain, reduce opioid consumption, and accelerate early ambulation in patients undergoing thoracoscopic lobectomy compared with PCIA alone.