Postoperative analgesia following robot-assisted thoracic surgery for mediastinal disease: retrospective comparative study of general anesthesia alone, combined with epidural analgesia, and with ultrasound-guided thoracic paraspinal block

Introduction

Since its launch in the early 1990s, the application of robot-assisted thoracic surgery (RATS) has been increased due to its less invasiveness, clearer three-dimensional visualization of the surgical field, greater precision, and easier accessibility of targets with more flexible devices than video-assisted thoracic surgery (VATS) or open thoracotomy (1,2). In the last decade, RATS have been amply proven in its feasibility and safety (3,4). Although VATS has been found as being better than open thoracotomy in terms of its lesser invasiveness (5,6), and RATS is associated with a shorter hospital stay and fewer postoperative complications than thoracotomy (7), RATS requires fewer emergency conversions to open thoracotomy and is associated with lower mortality compared with VATS (1,8).

However, despite the benefits of RATS, postoperative pain following RATS had not been well investigated. We previously performed a retrospective study comparing thoracic epidural analgesia (TEA) and patient-controlled analgesia (PCA) combined with intercostal block (ICB) via the surgical field for postoperative pain in patients who underwent RATS. We concluded that TEA was a more appropriate analgesic method than intravenous (IV) PCA with ICBs via the surgical field (9).

In the previous study, we pointed out that a limitation of the study was that we evaluated RATS for lung resection as well as mediastinal disease together, and we could not evaluate analgesia separately for the two types of disease entities. Therefore, in this study, we investigated postoperative pain, focusing on RATS for mediastinal disease. We present the following article in accordance with the STROBE reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4258/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), and was approved by the institutional ethics board of Juntendo University Hospital (No. 19-123). The need for patients’ informed consent was waived for this retrospective research.

Patients

The consecutive 172 patients scheduled to undergo RATS at Juntendo University hospital from January 2019 to December 2021 were registered. They were anesthetized with either general anesthesia alone (Group non-block; Group NB), general anesthesia combined with thoracic epidural anesthesia (Group TEA), or general anesthesia combined ultrasound-guided thoracic paraspinal blocks (TB), at the discretion of the attending anesthesiologist. Accordingly, postoperative analgesia was provided either by IV-PCA (NB), TEA, or ultrasound-guided TB, as mentioned below. Based on the primary methods of postoperative analgesia, the patients were divided into three groups: Groups NB, TEA, and TB, and the intensities of postoperative pain were compared among the three groups.

Anesthesia method and postoperative analgesia in Group NB

General anesthesia induction and maintenance were performed with total intravenous anesthesia (TIVA) using a target-controlled infusion of propofol (1.5–3 µg/mL) and continuous infusion of remifentanil (0.1–0.4 µg/kg/min). The flow rate of TIVA was adjusted using the bispectral index (BIS) between 40 and 60 to ensure hemodynamic stability during the anesthetic period.

Rocuronium was administered intermittently to acquire muscle relaxation for tracheal intubation and surgical field. Fentanyl was administered if required. A standard left-sided double-lumen tube was used to achieve one-lung ventilation (OLV). In twenty-three cases, the surgeons performed local anesthetic infiltration with 0.25% levobupivacaine (3–10 mL) at the commencement of surgery. If postoperative IV-PCA was needed based on the anesthesiologist’s decision, a disposable PCA pump (Coopdech Syrinjector PCA Set^®, Daiken Medical, Tokyo, Japan). It was filled with fentanyl (1,000 µg/20 mL) and normal saline (20 mL) to compound to fentanyl 25 µg/mL of fentanyl. The continuous infusion rate, bolus dose, lockout time, and hourly limit were adjusted to 1 mL/h, 1 mL, 10 min, and 7 mL, respectively, The continuous infusion commenced at the end of surgery after several boluses of fentanyl to achieve appropriate early postoperative analgesia. The continuous infusion was quit on POD 1 or 2.

Anesthesia method and postoperative analgesia in Group TEA

A thoracic epidural catheter was inserted via a mid-thoracic (5/6 or 6/7) intervertebral space with the loss of resistance technique of normal saline. The loss of cold sensation 5 min after injection2ml of 2% lidocaine was performed to confirm the effect of epidural analgesia. General anesthesia induction and maintenance were performed with TIVA using propofol and remifentanil, as mentioned above. Rocuronium was administered intermittently to acquire muscle relaxation for tracheal intubation and surgical field. Fentanyl was administered if required. A combination of 0.25% levobupivacaine (4 mL), fentanyl (50 µg), or morphine (1–2 mg) was administered through the epidural catheter. A disposable infusion pump with a PCA function (bolus dose, 3 mL; lockout time, 30 min) (Rakuraku Fusor^®, Smiths Medical Japan, Tokyo, Japan) was filled with 0.25% levobupivacaine alone, or combined with morphine (2–6 mg) or fentanyl (400–600 µg), at the anesthesiologists’ discretion. Continuous infusion through epidural catheter was started at a rate of 3 mL/h during surgery. The continuous infusion was quit on postoperative day (POD) 1 or 2.

Anesthesia method and postoperative analgesia in Group TB

TBs were performed via one to three intercostal spaces (T3–8) on the surgical side using an ultrasound guidance technique before general anesthesia induction. The loss of cold sensation 5 min after injection of 0.25% levobupivacaine (10–50 mL) was performed to confirm the effect of the thoracic blocks. General anesthesia induction and maintenance were performed with TIVA using propofol and remifentanil, as mentioned above. Rocuronium was administered intermittently to acquire muscle relaxation for tracheal intubation and surgical field. If postoperative IV-PCA was needed based on the anesthesiologist’s decision, the same disposable PCA pump settings as in the NB Group was used and continued until POD 1 or 2.

Surgical procedures of RATS

Robotic surgery for mediastinal diseases was performed via the lateral thoracic intercostal approach using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) with a three or four-arm technique, via incisions placed between the 3rd and 7th intercostal spaces. Additionally, one or two VATS camera ports were inserted via the same intercostal spaces as the robot arms. The patients were positioned in the supine position. During OLV, artificial pneumothorax of 5 to 12 mmHg was achieved with CO₂ insufflation. In the end of surgical procedure, one or two chest drains were inserted via the most dorsal port, which were removed after confirmation of no air leakage the drainage volume of less than 300 mL/24 h.

Data collection

Parameters of patients’ demographics, anesthesia, surgery, postoperative pain, side effects of anesthesia and analgesia, and clinical outcomes were studied and compared among the three groups. Drug uses of fentanyl and acetaminophen during anesthesia, surgical time, anesthetic time, surgical bleeding, and intraoperative fluid volume were investigated from the patient’s anesthetic records. Data on patients’ demography and comorbidities, surgical procedures, intensity of postoperative pain at rest evaluated by the ward nurses on a numerical rating scale (NRS) (0: no pain, 10: worst pain imaginable) at 0, 3, 6, 12, 18, 24, and 48 h postoperatively, rescue analgesic [IV pentazocine (30 mg), acetaminophen (1,000 mg), or flurbiprofen (50 mg)] requirements within 24 h postoperatively, major side effects (respiratory depression), and minor side effects (hypotension, defined as systolic blood pressure <90 mmHg, nausea requiring antiemetic therapy, urinary retention, and pruritus) were recorded within 24 h after surgery, time to ambulation after surgery, and hospital stay after surgery were investigated from the medical records.

Statistical analysis

SPSS 25.0 software (SPSS, Chicago, IL, USA) was used for statistical analysis. All variables are shown according to the methods of descriptive statistics (mean and SD or frequency). The distribution of variables was examined for normality using the Kolmogorov-Smirnov test. Levene’s test was used to assess the equality of variance in the different samples. In order to test differences between means, ANOVA was applied in the case of normal distribution. Categorical data were compared with Fisher’s probability test or chi-square test; otherwise, the Kruskal-Wallis test was used. Intra-group differences were tested with repeated measures ANOVA. Post-hoc tests were performed by using Bonferroni and/or Tukey’s correction, as appropriate. A value of P<0.05 was considered statistically significant. A sample size calculation to identify a 1.0 difference in the NRS scores based on the SD value of 1.3 reported in a previous study indicated that 17 patients would be required per group, and the total number of patients required for three groups was 68, with an α of 0.05 in a two-sided test and a power of 0.8 (10).

Results

During the study period, 172 patients were scheduled to undergo for RATS. In 2 patients of them, since RATS was intraoperatively converted to open thoracotomy, 170 patients were enrolled in the study. Of them, 25 patients received local anesthetic infiltration/ICB via the surgical field by the surgeon, 103 received TEA with only levobupivacaine (n=18), levobupivacaine with fentanyl (n=15) or levobupivacaine with morphine (n=70), and the remaining 42 patients received ultrasound-guided TBs, which included thoracic paravertebral block (TPVB, n=1) (11), erector spinae plane block (ESPB, n=8) (12-14), and midpoint transverse process (MTP, n=33) to pleura block (15). However, since the epidural catheter was accidentally removed in one patient data from 169 patients (25 in Group NB, 102 in Group TEA, and 42 in Group TB) were analyzed (Figure 1).

Figure 1 Flow chart of patients included in this study.

The number of patients in each group was confirmed to be more than the required sample size calculated by a priori power analysis.

All patients in the three groups were extubated immediately after surgery in the operating room. Demographic and surgical data were not different between the three groups (Table 1). The doses of fentanyl required during anesthesia were significantly different among the three groups and the frequency of acetaminophen administration at the end of surgery was significantly lower in the TEA group than in the other groups. The incidence of patients who used rescue analgesics within 24 h was significantly lower in the TEA group than the other groups. The frequencies of IV-PCA usage were almost the same in the NB and TB groups (76% and 76.2% respectively) (Table 2). In the TB group, the mean (SD) volume of 0.25% levobupivacaine injected was 27.9±6.5 [10–50] (Table 2).

NRS pain scores at 6 and 12 h were significantly lower in Group TEA than in NB. Additionally, NRS scores in Group TEA tended to be lower than those in Group TB at 6 and 12 h (Table 3, Figure 2). In terms of intragroup changes, pain scores in the NB group at 48 h were significantly lower than those at 0, 3, 6 and 12 h (P<0.05); pain scores in the TEA group at 0 h were significantly higher than those at 6, 18, 24 and 48 h (P<0.05); and pain scores in the TB group at 0 and 3 h were significantly higher than those at 24 and 48 h (P<0.05) (Table 3). The incidences of side effects for 24 h, except for PONV, there were not significantly different between the three groups in time to ambulation and hospital stay after surgery. The incidence of PONV was significantly lower in Group TB versus Groups TEA and NB (2.4% vs. 18.6% and 28%, respectively, P<0.01) (Table 4).

Figure 2 Postoperative pain scores. NB, non-block; TEA, thoracic epidural analgesia; TB, thoracic paraspinal block.

Discussion

Recently, the number of RATS for lung resection has been increasing, while the number of open thoracotomies is decreasing and the number of VATS remains almost the same (7). Although RATS is being increasingly performed, only a couple of previous researches evaluated the intensity of postoperative pain after RATS (10,16). A recent article reported that RATS and VATS in patients with non-small cell lung cancer are not significantly different in terms of postoperative and long-term pain (2 weeks, 3 months, 6 months, and 1 year), and mean pain scores remained below three at all time points in both groups. Additionally, since those patients were anesthetized with only general anesthesia without any postoperative analgesic methods, the authors concluded that both RATS and VATS are relatively painless procedures (17). On the other hand, compared to thoracotomy for lung resection, postoperative pain scores at 3 weeks are reportedly lower following RATS (2.5 vs. 4.4, P=0.04) (18), although according to van der Ploeg et al., there are no differences in pain between open thoracotomy, VATS, and RATS for lung resection (19). Recent studies comparing the pain after RATS and open thoracotomy for lung resection illustrated that acute postoperative pain after RATS remained as intense as that after open thoracotomy until POD 3, although it was less intense on POD 4 and later, compared with open thoracotomy (10,16). Thus, surgeons believe that RATS might be relatively painless, although there is no evidence to support this.

Surgery for mediastinal diseases is performed via one of three approaches: sternotomy, VATS, and RATS. However, unlike RATS for lung resection, there is not much evidence on outcomes following RATS for mediastinal diseases. A previous study used a large, national database to compare VATS vs. RATS for mediastinal tumor resection in terms of short-term perioperative outcomes and long-term survival. In that study, RATS resection was associated with improved short-term outcomes, including 90-day mortality, 30-day unplanned readmission, positive pathology margin, conversion to open procedure, and composite outcomes compared with VATS resection for mediastinal tumors (20). Unfortunately, however, perioperative pain has never been addressed. Thus, our study is the first study to focus on pain after RATS for mediastinal disease.

Generally, appropriate postoperative pain management after thoracic surgery is essential to reduce the risk of postoperative complications as well as to improve patient satisfaction (16,19,21,22). Further, appropriate postoperative pain management after thoracic surgery may possibly reduce the incidence of chronic post-thoracotomy pain syndrome (23). Our data suggest that intensive postoperative analgesic methods used for open thoracotomies and VATS, such as TEA and thoracic blocks, might also be appropriate for controlling pain following RATS for mediastinal tumors, at least during the early postoperative period. Even though there were significant differences between NB and TEA at 6 and 12 h after surgery, the differences are so slight in the low scores, whether clinically relevant should be investigated in the next prospective study.

Since artificial pneumothorax, which is required for RATS, occasionally induces severe intraoperative hypotension (24), unilateral TB or NB might be superior to TEA with local anesthetics alone in terms of circulatory stability during RATS, since epidural local anesthetics can also cause severe hypotension due to bilateral reduction of thoracic sympathetic tone (25). In this study, although only in TEA group, 8 patients experienced postoperative hypotension, while the other groups were not, the incidence of postoperative hypotension was not significantly different among the groups (P=0.06). This is possible because our TEA method successfully reduced the amount of local anesthetic administered by combining epidural opioids with local anesthetics in most patients (84/102) in Group TEA.

On the other hand, patients of Groups NB and TEA experienced a greater frequency of PONV for 24 h postoperatively than Group TB. This could be because the intraoperative dose of fentanyl was much higher in the NB group than in the other groups, even though the incidences of postoperative IV-PCA usage were the same in Groups NB and TB. This observation could also reflect the fact that epidural opioids were administered in most patients in Group TEA. This suggests the need for improving PCA regimes, such as by using dexmedetomidine (26), or for improving TEA regimes by omitting opioids. In this study, TB seemed to be superior to the other analgesic methods.

The present study has several limitations. First, the retrospective study design might be associated with limitations in terms of collecting accurate and/or important data. Further prospective studies on RATS for the mediastinal disease are required to confirm the ideal analgesic method. The second limitation of the study is that there was no standard baseline analgesia protocol. Indeed, intraoperative acetaminophen was not administered basally in all patients. NSAIDs were given as rescue medication in the postoperative period but not pre- or intraoperative period. Since systemic basal pre- or intraoperative analgesia with acetaminophen and NSAIDs is recommended by some scientific societies, we should reconsider our protocol in the near future. Third, the subxiphoid approach, which is not included in this study, is another surgical approach for RATS for mediastinal disease. The two approaches, the lateral thoracic intercostal approach and subxiphoid approach, might have different invasiveness and postoperative pain. In the future, both these approaches should be investigated. And lastly, this study may be small enrollment to state something about side effects. We should increase the patients’ number in the next study.

Conclusions

Compared with NB, TEA provided better postoperative analgesia in patients who underwent RATS for mediastinal disease via the lateral thoracic intercostal approach. Thoracic blocks also seem to be appropriate for postoperative analgesia, providing almost equivalent pain relief as TEA, with low postoperative NRS scores. Additionally, thoracic blocks were associated with a significantly lower frequency of PONV for 24 h after surgery compared to NB and TEA. Thus, thoracic blocks might also provide adequate postoperative analgesia following RATS for mediastinal disease.

Acknowledgments

We thank all the staff contributing to the practice of robot-assisted thoracic surgery.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-22-4258/rc

Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-4258/dss

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-4258/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4258/coif). IK serves as an unpaid Editorial Board Member of Annals of Translational Medicine from April 2022 to March 2024. 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 conducted in accordance with the Declaration of Helsinki (as revised in 2013), and approved by the institutional review board of Juntendo University Hospital (protocol No. 19-123). The need for individual consent for this retrospective analysis was waived.

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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