The Effect of Combined General Anesthesia and Epidural Analgesia on Postoperative Pulmonary Complications in Thoracoscopic Esophagectomy

TL;DR

This study examines whether using combined general anesthesia and epidural analgesia reduces postoperative lung issues in patients undergoing thoracoscopic esophagectomy.

Contribution

The study is the first to investigate the impact of epidural analgesia on postoperative pulmonary complications in thoracoscopic esophagectomy.

Findings

Epidural analgesia did not significantly reduce postoperative pain or pneumonia rates.

Patients receiving epidural analgesia had differences in cancer type, lymphocyte counts, and comorbidities.

No significant difference in hospital stay duration was observed between groups.

Abstract

Background and Aims: Although combined general anesthesia and epidural analgesia are used in open surgery to promote rehabilitation and expectoration, as well as to prevent postoperative pulmonary complications, their effect in thoracoscopic esophagectomy remains unclear. This study aimed to address this issue. Patients and Methods: We enrolled 150 patients who underwent thoracoscopic esophagectomy between May 2017 and July 2025. Patient characteristics and postoperative outcomes, including maximum numerical rating scale (NRS) after surgery and pneumonia, were compared between the use and non-use of epidural analgesia. Epidural analgesia was not administered in patients using antithrombotic/anticoagulant drugs or in those with a history of thoracic spine surgery. Postoperative analgesia involved the scheduled administration of acetaminophen in all cases, with patient-controlled analgesia using opioids administered to the non-epidural analgesia group. Results: Epidural analgesia was administered to 113 patients (75.3%). The most common levels of epidural catheter placement were Th8/Th9 in 55 patients (36.7%) and Th7/Th8 in 41 patients (27.3%). Laparoscopy was performed in 129 patients (86.0%). Median NRS was five, and pneumonia occurred in 16 patients (10.7%). The epidural anesthesia group had a higher proportion of squamous cell carcinoma (88.5% vs. 73.0%, p = 0.024), lower lymphocyte counts (1680 vs. 2065, p = 0.020), diabetes (16.8% vs. 37.8%, p = 0.007), and hypertension (54.9% vs. 81.1%, p = 0.006), and circular stapler anastomosis (83.2% vs. 62.2%, p < 0.001). No significant differences were observed in the postoperative NRS, pneumonia, or length of postoperative hospital stay. Conclusions: There was no significant difference in the postoperative NRS and pneumonia between those with or without epidural analgesia in thoracoscopic esophagectomy.

Full text

1. Introduction

Esophagectomy is the cornerstone of curative treatment for esophageal cancer. However, complications are frequent owing to surgical invasion extending into the thoracic and abdominal regions [1], and postoperative pneumonia, in particular, has been reported to worsen the prognosis [2,3]. In this regard, various perioperative management strategies using a multidisciplinary team approach are recommended to reduce the postoperative complications of esophageal cancer [4].

Among these, combined general anesthesia and epidural analgesia during esophagectomy with open thoracotomy and laparotomy is performed to promote rehabilitation and expectoration through postoperative analgesia and to prevent postoperative pneumonia [5]. However, in recent years, minimally invasive thoracoscopic esophagectomy has become widespread, with over half of esophagectomies in Japan now performed thoracoscopically [6]. The efficacy of combined general anesthesia and epidural analgesia in reducing postoperative complications during thoracoscopic esophagectomy remains unclear.

This study aimed to clarify the effect of combining general anesthesia with epidural analgesia in reducing postoperative complications during thoracoscopic esophagectomy for esophageal cancer. The primary endpoint was postoperative pneumonia, and the secondary endpoint was other postoperative complications and length of hospital stay.

2. Patients and Methods

This study included 150 patients who underwent thoracoscopic esophagectomy for esophageal cancer between May 2017 and July 2025. Epidural analgesia was not performed in patients using antithrombotic or anticoagulant drugs, or in those with a history of thoracic spine surgery. The placement site of the epidural catheter was determined at the discretion of the anesthesiologist. After epidural catheter placement, the anesthesiologist administered general anesthesia with continuous intravenous infusion of remifentanil at 0.25 μg/kg/min and continuous epidural infusion of 0.25% levobupivacaine for analgesia. The surgery involved right thoracoscopy in the prone position with intrathoracic lymph node dissection, laparoscopic gastric mobilization in the supine position with lymph node dissection, reconstructive gastric tube creation, pulling up to the neck, and cervical anastomosis. Postoperatively, the patient was admitted to the intensive care unit for mechanical ventilation. Extubation was performed the day after surgery, and rehabilitation was initiated. Postoperative analgesia consisted of continuous epidural anesthesia and scheduled intravenous acetaminophen (1000 mg every 8 h) for 5 days [7]. Opioid patient-controlled analgesia was administered as non-epidural anesthesia.

Evaluation parameters included patient background (surgery year periods, sex, age, body mass index, underlying disease, serum albumin level, lymphocyte count, C-reactive protein level, esophageal cancer stage (TNM 8th) [8], and preoperative treatment), surgical variables (mediastinoscopy use [9], laparoscopic manipulation, reconstruction route, reconstructed organ, and anastomosis method), time from entering the operating room to starting surgery and after-hours surgery (time exceeding regular working hours), severity of postoperative pain assessed using the maximum numerical rating scale (NRS) over the first 3 days after surgery, and postoperative complications based on Clavien–Dindo classification [10]. Grade 2 or higher (recurrent laryngeal nerve palsy, pneumonia, anastomotic leakage, wound infection, distant infection, urinary tract infection, and catheter-related infection), and postoperative length of stay, were retrospectively examined. They were classified and compared based on the use or non-use of epidural anesthesia. Pneumonia was defined as a case with symptoms such as fever, cough, and sputum, with infiltration shadows on chest X-Ray or CT, and blood test findings such as elevated white blood cells and CRP levels, and antimicrobial treatment.

Pearson’s chi-squared test was used for categorical variables, and the Mann–Whitney U test was used to evaluate differences in continuous variables. All analyses were performed using JMP 13 (SAS Institute Inc., Cary, NC, USA), with statistical significance set at p  <  0.05. The study was approved by the Institutional Review Board of Kochi Medical School (ERB-111984).

3. Results

Table 1 shows patient characteristics and comparisons based on the presence or absence of epidural analgesia. The median age was 71 years, and 125 patients (83.3%) were male. Forty-eight percent of all patients had Stage III or IV (advanced) cancer, and 46% received preoperative chemotherapy. The most common underlying diseases were hypertension (61.3%), chronic obstructive pulmonary disease (32.7%), cardiovascular disease (28.0%), and diabetes (22.0%). Robot-assisted surgery was performed in 66 patients (44.0%), hybrid combined mediastinoscopy and right thoracoscopy in 53 (35.3%), and laparoscopic gastric mobilization for abdominal procedures in 129 (86.0%). Epidural anesthesia was administered to 113 (75.3%) patients. The time to the start of surgery, operative time, and after-hours surgery time were 89 min, 575 min, and 146 min, respectively. Median postoperative maximum NRS was five, and pneumonia occurred in 16 patients (10.7%) (Table 2).

Table 3 shows a comparison of outcomes between the use and non-use of intraoperative epidural anesthesia. When categorized by surgical year into early (2017–2021, n = 70) and late (2022–2025, n = 80) periods, epidural analgesia was administered to 58 of 70 cases (82.9%) in the early group and 55 of 80 cases (68.8%) in the late group (p = 0.046). There was no significant difference in age at the period (Early group 70 years vs. Late group 71 years, p = 0.210) or anticoagulant use (Early group 12.9% vs. Late group 17.5%, p = 0.431). The levels of epidural catheter insertion were Th8/Th9 in 55 patients (36.7%) and Th7/Th8 in 41 patients (27.3%). No hematomas or infectious complications associated with the epidural catheter were observed.

Those who received epidural analgesia showed a higher proportion of squamous cell carcinoma histology (88.5% vs. 73.0%, p = 0.024) and higher lymphocyte counts in blood tests (1680/μL vs. 2065/μL, p = 0.020) than those who did not receive epidural analgesia. Comorbidities were more common in the non-epidural anesthesia group, with statistically significant differences in the prevalence of diabetes (16.8% vs. 37.8%, p = 0.007) and hypertension (54.9% vs. 81.1%, p = 0.006). The reconstruction route was more frequently retrosternal in the epidural analgesia group and posterior mediastinal in the non-epidural anesthesia group. Circular stapler anastomosis was more frequently used (83.2% vs. 62.2%) in the epidural analgesia group, whereas other anastomosis methods were more common in the non-epidural analgesia group. Preoperative treatment was more frequent in the epidural analgesia group, although the difference was not significant.

No significant differences were observed between the two groups in terms of the proportion of laparoscopic procedures, operative time, blood loss, intraoperative fluid administration, maximum NRS, postoperative complication rates, or length of postoperative hospital stay. After excluding the use of antithrombotic or anticoagulant drugs, no significant difference in the incidence of postoperative pneumonia was observed between the epidural analgesia group and the non-epidural analgesia group (10.9% vs. 0.0%, p = 0.152). Robot-assisted surgery was slightly more common in the group without epidural analgesia (39.8% vs. 56.8%; p = 0.072); however, no significant difference was observed between the presence or absence of robot-assisted surgery and NRS (5 vs. 5; p = 0.846) or the incidence of postoperative pneumonia (12.1% vs. 9.5%; p = 0.608). The group with an epidural catheter placed preoperatively on the day of surgery trended to have a longer time to the start of surgery (84 min vs. 92 min, p = 0.111) and after-hours surgery (111 min vs. 155 min, p = 0.095). There was no significant difference between the epidural catheter placement level and postoperative pain scores, and postoperative pneumonia (Table 4).

Patients with postoperative pneumonia had a higher prevalence of diabetes compared to those without pneumonia (50.0% vs. 18.7%, p = 0.004) and a lower rate of NAC (12.5% vs. 50.0%, p = 0.004). In multivariate logistic analysis, patients with diabetes (odds ratio: 4.217; 95% confidence interval (CI): 1.384–12.843; p = 0.011) were significant risk factors for pneumonia, and neoadjuvant chemotherapy (NAC) tended to reduce the risk (odds ratio: 0.147; 95% CI: 0.031–0.685; p = 0.015).

4. Discussion

In conventional open gastrointestinal surgery, the combination of general and epidural anesthesia has been considered to promote postoperative recovery by alleviating postoperative pain and suppressing protein catabolism [11]. In esophagectomy, reports indicate that the combination of general and epidural anesthesia not only provides postoperative analgesia but also suppresses the elevation in inflammatory stress hormones [12]. Meta-analyses of esophagectomy have reported that epidural analgesia not only aids respiratory recovery and shortens intensive care unit stay through postoperative analgesia [13] but also reduces pulmonary complications [14]. However, this may have been influenced by the shift from traditional open thoracotomy and laparotomy to minimally invasive surgery via thoracoscopy and laparoscopy [15].

It was previously reported that inserting an epidural catheter at the Th7/Th8 level significantly reduced postoperative pain compared to placement over Th6/Th7 or Th8/Th9 during esophagectomy. However, in thoracoscopic surgery combined with laparoscopic surgery, epidural catheter placement under Th8/Th9 significantly increases postoperative pain [16]. This suggests that in esophagectomy involving both thoracic and abdominal procedures, the effect of epidural analgesia on reducing postoperative pulmonary complications may be limited in thoracoscopic surgery compared with open surgery. Therefore, a PubMed search using the keywords [thoracoscopic esophagectomy] and [epidural anesthesia] yielded the results shown in Table 5 [17,18,19,20]. Studies reported that inserting an epidural catheter at a level higher than Th7 resulted in a reduction in pulmonary complications compared to intravenous analgesia [18], whereas studies reported that inserting it below Th7 showed no reduction in pulmonary complications [17,20].

A randomized controlled trial comparing thoracoscopic and open surgery for esophagectomy demonstrated a reduction in pulmonary complications with thoracoscopic surgery [21]. Conversely, the ROMIO randomized clinical trial comparing open surgery with laparoscopic or open abdominal procedures found no difference in postoperative complication rates between the open and laparoscopic approaches [22]. A real-world study using the Japanese national clinical database also compared abdominal procedures during thoracoscopic esophagectomy between the open and laparoscopic approaches and found no significant differences in pulmonary complication rates [23]. These findings suggest that minimizing thoracic wall damage via thoracoscopy and providing thoracic analgesia through high-level epidural anesthesia are more important than abdominal analgesia for reducing pulmonary complications. In this study, 46 of the 113 patients who received epidural analgesia had a catheter placement of Th7/Th8 or above, and 67 (59.3%) had Th8/Th9 or below; however, there was no significant association between epidural catheter placement level and postoperative pain scores, and postoperative pneumonia. We initiated open thoracotomy and total laparoscopic gastric mobilization in 2005 [24], switching to combined thoracoscopic and laparoscopic techniques in 2009. However, because we performed a small laparotomy in the epigastrium to confirm blood flow in the reconstructed gastric conduit using near-infrared fluorescence after laparoscopic gastric mobilization [25], the difference in postoperative pain between the open and laparoscopic approaches may have been reduced. The use of additional analgesic methods, including scheduled intravenous acetaminophen [7], may have influenced the incidence of postoperative pulmonary complications based on the use or non-use of epidural analgesia. Moreover, the aging patient population has increased the prevalence of concomitant atrial fibrillation, leading to an increasing trend in patients using thromboembolic prophylaxis and anticoagulants [26]. Since epidural anesthesia is contraindicated in these patients, diverse analgesia methods are crucial, such as performing wound infiltration anesthesia by injecting a local anesthetic into the surgical site before surgery concludes [27]. Furthermore, if after-hours surgery can be reduced by omitting epidural catheter insertion, it may lead to a reduction in labor costs.

The limitations of this study include the biases inherent to retrospective, small-sample, comparative research. For example, the non-epidural analgesia group had a higher prevalence of underlying comorbidities, such as hypertension and diabetes, use of antithrombotic or anticoagulant drugs, a higher proportion of robotic surgeries, and higher lymphocyte counts. These factors may have influenced surgical invasiveness and patient immunity, and these patients inherently have a higher perioperative risk. Also, time-related heterogeneity about advance of the surgical techniques, perioperative care, enhanced recovery protocols, and anesthesia practice might affect the postoperative complications.

In addition, the placement site of the epidural catheter and the physicians performing the catheter insertion were not standardized. Due to the limited number of subgroup samples at the epidural catheter level, statistical power was insufficient. Furthermore, while the protocol of the postoperative opioid administration was established, the quantified dosage (total mg) used by each patient was not retrospectively available. Data were also unavailable regarding the use of rescue analgesics, the incidence of postoperative nausea and vomiting, and the duration of ileus.

5. Conclusions

In this study, there was no significant difference in the complication rate of postoperative pneumonia with or without epidural analgesia during thoracoscopic esophagectomy. Omitting epidural analgesia may lead to more efficient utilization of medical resources and the length of time involved in esophagectomy; however, further accumulation of cases and investigations is necessary to reveal this.