Efficacy and safety of intercostal nerve block for postoperative analgesia in patients with stage III tuberculous empyema: a retrospective study based on propensity score matching

Introduction

Stage III tuberculous empyema is defined by irreversible pathological alterations, including fibrosis of the empyema cavity wall and pleural calcification. These changes frequently precipitate secondary thoracic deformities, such as chest wall collapse, spinal scoliosis, and compression of the lung parenchyma. Beyond the significant physiological impairments these complications entail, patients also experience a substantial psychological burden (1). In clinical practice, traditional thoracotomy and video-assisted thoracoscopic surgery (VATS) with lesion debridement and pleural decortication are mainstay interventions aimed at improving patient outcomes (2). However, the optimization of postoperative acute pain management and the development of effective analgesic strategies remain pressing clinical challenges (3). Previous research has firmly established a direct correlation between the extent of surgical trauma and the intensity of postoperative pain (4). Compared with minimally invasive VATS procedures, surgeries for tuberculous empyema typically involve more extensive tissue disruption, resulting in more severe postoperative incisional pain (5). Moreover, the routine use of opioids for postoperative analgesia presents notable risks. Unmanaged acute postoperative pain can progress to chronic pain syndromes, potentially leading to a cascade of complications, including chest tightness, dyspnea, diminished lung function, and anxiety or depression. Collectively, these sequelae significantly compromise patients’ quality of life (6). Intrapleural administration of ropivacaine for intercostal nerve block (INB) has emerged as a promising approach in managing acute postoperative pain following thoracic surgeries, effectively reducing pain scores and minimizing opioid requirements (7). Despite these advances, there is a paucity of clinical research focusing on postoperative analgesic regimens specifically tailored to patients with stage III tuberculous empyema (8). Existing studies in this area are often hampered by selection bias and confounding variables, limiting their generalizability and clinical utility. To bridge these knowledge gaps, this retrospective study included patients with stage III tuberculous empyema who underwent surgical treatment at Xi’an Chest Hospital. By employing propensity score matching (PSM) to standardize baseline characteristics across study groups, our objective was to conduct a comprehensive assessment of the efficacy and safety profiles of various analgesic protocols. The findings of this study aim to inform and optimize postoperative analgesic strategies in clinical settings, ultimately enhancing patient care and outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1308/rc).

Methods

Study design and participants

This study retrospectively analyzed the clinical data of 315 patients with stage III tuberculous empyema who were screened from 833 cases of tuberculous empyema (including stages I, II, and III) admitted to Xi’an Chest Hospital from August 9, 2020 to March 25, 2025. The patients were divided into group A and group B according to different analgesic regimens (detailed below). Additionally, sensitivity analyses were conducted by excluding data from the first two years of the study period to account for potential impacts arising from advancements in anesthetic and surgical techniques during this initial phase. The inclusion criteria (9,10) were as follows: (I) preoperative diagnosis of stage III tuberculous empyema confirmed by chest computed tomography (CT) (showing stage III-specific imaging features) combined with pathological and/or etiological evidence (from puncture specimens if available) confirming tuberculous infection, with both modalities collectively establishing the stage III classification; postoperative diagnosis was further validated by surgical specimens, while enrollment was strictly based on preoperative assessment; (II) lesions involving three or more ribs; (III) chest CT showing typical stage III features: irreversible fibrosis of the empyema cavity wall, pleural calcification, thoracic deformities (e.g., chest wall collapse, rib crowding), significant pleural thickening on the affected side, and compressed lung tissue with restricted expansion; (IV) newly diagnosed patients receiving regular anti-tuberculosis treatment for more than three months before surgery, and previously treated patients receiving treatment for more than two weeks before surgery. The exclusion criteria were: (I) chest CT showing severe intercostal space stenosis or even imbricated rib changes; (II) chest CT indicating the need for lobectomy due to concomitant ipsilateral lung lesions; (III) chest CT showing extensive serrated adhesions or incarceration between the thickened pleura and lung tissue; (IV) concomitant severe underlying diseases affecting surgical safety (such as HIV infection, severe malnutrition); (V) concomitant active pulmonary tuberculosis; (VI) concomitant lung malignancy. The specific screening of cases is shown in Figure 1. All patients underwent routine pre-operative examinations, including electrocardiogram, pulmonary function test, echocardiogram, and erythrocyte sedimentation rate. On the first day after surgery, a complete blood count was rechecked, and chest CT scans were performed on the second to third postoperative days based on individual patient conditions. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Xi’an Chest Hospital (Approval R2023-004-01) and individual consent for this retrospective analysis was waived.

Figure 1 Study flow chart of patient inclusion. HIV, human immunodeficiency virus; INB, intercostal nerve block; NRS, Numerical Rating Scale; PCIA, patient-controlled intravenous analgesia; PSM, propensity score matching.

Data collection

Data were extracted from the hospital’s electronic information system. Demographic characteristics were collected upon admission, comorbidities were determined through patient self-reporting or previous diagnoses, and surgical-related information was obtained from operative records, anesthesia records, and nursing notes. The data collected included: (I) demographic characteristics: gender, age, body mass index (BMI), smoking history; (II) tuberculosis-related data: pulmonary tuberculosis, anti-tuberculosis treatment regimens [standard quadruple therapy with isoniazid, rifampicin, pyrazinamide, and ethambutol (H-R-Z-E), non-standard H-R-Z-E regimens]; (III) comorbidities: diabetes mellitus, hypertension, coronary heart disease; (IV) surgical information: surgical site, surgical incision length, intercostal location of the incision, operative duration, intraoperative blood loss, number of drainage tubes.

Surgical technique and analgesic regimen grouping

Surgical procedure

All surgeries were performed under general anesthesia with double-lumen endotracheal intubation and one-lung ventilation of the healthy lung. Based on the abscess range detected by preoperative B-ultrasound, a posterior incision was created between the 5th and 8th intercostal spaces to access the thoracic cavity. The size of the incision was determined according to the size of the patient’s lesion, the difficulty of separating adhesions, and the surgeon’s operating habits (in case of incision extension during the operation, the final extended size was taken as the standard). If the intercostal space was narrow, the rib segment within the incision was resected, and access to the thoracic cavity was achieved through the rib bed. Subsequently, the operation continued with the resection of part of the parietal fibrous pleura beneath the incision to expose the empyema cavity. After entering the cavity, the contents were aspirated and collected for microbiological testing. Then, blunt dissection was carried out to thoroughly and carefully remove the visceral, parietal, and pleural fibrous layers. For patients with lesions around the lung parenchyma, lung wedge resection was performed as appropriate (cases undergoing lobectomy were excluded). Finally, adhesions between the lung and the anterior and posterior mediastinum were separated, and the lung was mobilized as much as possible. The thoracic cavity was then repeatedly irrigated with normal saline, and strict hemostasis was ensured. After the operation was completed, one or two thoracic drainage tubes were inserted according to the extent of the empyema and the condition of lung damage (one tube was placed in the upper thoracic cavity, and the other was located near the posterior costophrenic angle) to thoroughly drain the accumulated gas and fluid in the lung and promote lung re-expansion.

Analgesic regimens

(I) Before closing the thoracic cavity, centered on the intercostal space of the incision and spanning two intercostal spaces upward or downward (covering the intercostal space where the drainage tube was inserted), 0.2% ropivacaine (Shandong Ruiyang Pharmaceutical Co., Ltd., Approval No. H20183151, Ruiyang, China) was injected into the intercostal space using a 24G scalp needle under direct vision or with the assistance of thoracoscopy. Each intercostal space received an injection of 4 mL (Figure 2). (II) Postoperatively, all patients received patient-controlled intravenous analgesia (PCIA). The PCIA formula consisted of sufentanil citrate (Yichang Humanwell Pharmaceutical Co., Ltd., Approval No. H20054171, Yichang, China) at a dose of 2 µg/kg and tropisetron (Shanxi Pude Pharmaceutical Co., Ltd., Approval No. H20080601, Datong, China) 10 mg, diluted to 100 mL with normal saline. The bolus dose was 2 mL/h, the flow rate was 2 mL/h, the loading dose was 2 mL, and the lockout time was 15 min. (III) Oral analgesia: once the patient can tolerate oral intake, paracetamol (500 mg) combined with dihydrocodeine tartrate (10 mg) is administered orally. The dosage is 1–2 tablets every 4–6 hours, with a maximum of 2 tablets per administration and a daily maximum of 8 tablets. The analgesic protocols are as follows: group A: INB + PCIA + oral analgesics; group B: PCIA + oral analgesics.

Figure 2 Intercostal nerve block procedure prior to chest closure in stage III empyema. (A) The lower intercostal space undergoing blockade, demonstrating that the upper intercostal space remains non-distended prior to drug administration. (B) Blockade procedure in the upper intercostal space, showing pleural tissue disruption with potential drug leakage. (C) Post-injection status of ropivacaine in the upper intercostal space, exhibiting adequate intercostal distension. (D) Normal intercostal morphology of the thoracic cavity with well-defined anatomical landmarks.

Definition of outcome measures

(I) Pain intensity: assessed using the Numerical Rating Scale (NRS) (11), a 0–10 ordinal scale where 0 indicates no pain and 10 represents the worst possible pain. Key time-points for NRS assessment included: (i) mean NRS score within 24 hours post-operation (T1); (ii) peak NRS score post-operation (T2); (iii) NRS score upon thoracic drainage tube removal (T3). (II) Rescue analgesia use: defined as the number of administrations of opioid injectables (e.g., 10 mg morphine injection from Northeast Pharmaceutical Group, drug approval number H21021995) administered by anesthesiologists or surgeons from the postoperative follow-up team. Indications were inadequate pain control with PCIA plus oral medications (e.g., intractable breakthrough pain) and a resting NRS score ≥4. (III) Additional postoperative outcomes (12): 24-hour thoracic drainage volume, total thoracic drainage volume, time to thoracic drainage tube removal, time to discharge, and total hospitalization cost.

Statistical analysis

Data were analyzed using R version 4.3.2. Normally distributed continuous variables are presented as mean ± standard deviation and compared between groups using t-test. Non-normally distributed continuous variables are described as median (interquartile range) [M (Q₂₅, Q₇₅)] with group comparisons performed via Mann-Whitney U test. Categorical variables are reported as number of cases, constituent ratio/percentage, n (%) and analyzed using Pearson’s Chi-squared test. For missing data (accounting for <5% of total data points), single imputation was applied to maintain dataset integrity. PSM with a 1:1 ratio was conducted incorporating potential confounders including sex, age, BMI, lesion location, incision length, and operative time to evaluate postoperative outcomes. Post-matching comparisons focused on NRS pain scores, frequency of rescue analgesia, postoperative drainage volume, and duration of drainage tube indwelling. A caliper width of 0.2 was applied during matching, with statistical significance set at P<0.05. Sensitivity analysis was performed by excluding data from the first two years, and the same PSM methodology (1:1 ratio, caliper width 0.2, identical confounders) was applied to re-evaluate outcomes.

Results

Baseline characteristics of study participants

A total of 315 subjects were enrolled, including 54 in group A and 261 in group B. After 1:1 PSM, 49 subjects remained in each group. Missing data accounted for <5% of total data points across all baseline variables. Specifically, missing values were observed for the following variable: intraoperative blood loss (n=3) in the pre-matching cohort; no missing data were present in the post-matching cohort. All missing data were handled using single imputation to maintain dataset integrity. Before matching, baseline data showed imbalance between the groups, with significant differences in incision length (P=0.002), operation time (P=0.01), and intraoperative blood loss (P=0.04). Post-matching, no significant differences were observed in baseline characteristics, including BMI (P=0.93), gender (P=0.63), age (P=0.21), smoking history (P>0.99), hypertension (P=0.56), diabetes (P=0.48), coronary heart disease (P>0.99), concurrent pulmonary tuberculosis (P=0.41), use of H-R-Z-E anti-tuberculosis regimen (P=0.83), lesion site (P>0.99), intercostal location of incision (P=0.98), incision length (P=0.42), operation time (P=0.65), intraoperative blood loss (P=0.10), and number of thoracic drainage tubes (P=0.32) (Table 1). During the follow-up period, there were no cases of reoperation, death, empyema recurrence, or tuberculosis dissemination. Preoperative and postoperative CT imaging of representative patients (Figure 3) showed typical features of stage III tuberculous empyema, including compressed lung tissue, pleural thickening, and narrowed intercostal spaces preoperatively, with complete thoracic cavity expansion and near-normal intercostal spaces observed 3 months postoperatively.

Figure 3 CT images of a patient with stage III tuberculous empyema before and after surgery combined with intercostal nerve block. (A,C) Preoperative image (R: right side): compressed lung tissue, pleural thickening, and narrowed intercostal spaces are visible. (B,D) 3 months postoperatively (R: right side): complete expansion of the thoracic cavity and near-normal intercostal spaces are observed. CT, computed tomography.

Comparison of outcome indicators between group A and group B in patients with stage III tuberculous empyema after PSM

After PSM, among patients with stage III tuberculous empyema, the median 24-hour postoperative NRS score in group A was 2.00 (2.00, 3.00), significantly lower than 3.00 (2.00, 3.00) in group B (Z=−3.93; P<0.001); the median maximum postoperative NRS score was 3.00 (2.00, 4.00) in group A, lower than 4.00 (3.00, 4.00) in group B (Z=−2.80; P=0.005); the median NRS score after tube removal was 1.00 (0.00, 1.00) in both groups, with no significant difference (Z=−0.07; P=0.95); the median frequency of postoperative rescue analgesia was 0.00 (0.00, 0.00) in group A, significantly fewer than 0.00 (0.00, 1.00) in group B (Z=−2.43; P=0.02) (Figure 4). However, there were no significant differences in 24-hour postoperative thoracic drainage volume (P=0.43), total postoperative thoracic drainage volume (P=0.10), indwelling time of thoracic drainage tube (P=0.92), postoperative discharge time (P=0.64), and total hospitalization cost (P=0.49) between the two groups (Table 2).

Figure 4 Twenty-four-hour postoperative NRS scores, maximum postoperative NRS scores, post-extubation NRS scores, and frequency of postoperative rescue analgesia in group A and group B. Group A: INB + PCIA + oral medications; Group B: PCIA + oral medications. INB, intercostal nerve block; NRS, Numerical Rating Scale; PCIA, patient-controlled intravenous analgesia.

Sensitivity analysis

After excluding data from patients who underwent stage III tuberculous empyema surgery in the first two years, we performed PSM and comparisons following the original grouping. The results demonstrated statistically significant differences between group A and group B in the 24-hour postoperative NRS score (P<0.001), maximum postoperative NRS score (P<0.001), NRS score after tube removal (P=0.03), and frequency of postoperative rescue analgesia (P=0.006). These findings were consistent with the original results without substantial changes (Table S1).

Discussion

Stage III tuberculous empyema is characterized by marked thickening of the pleural fibrotic plate, which can tractionally deform the chest wall and compress lung tissue. Surgical intervention is critical for lesion debridement, recurrence prevention, thoracic deformity correction, and lung re-expansion (13). Traditional thoracotomy, limited by extensive incision trauma, has been increasingly supplanted by thoracoscopic techniques in recent years. Zhou et al. (14) developed curved retractable electrocoagulating hooks and pleural decortication instruments, facilitating the widespread adoption of thoracoscopic-assisted small incisions, uniportal, and biportal approaches, which have proven clinical efficacy (15,16). Although thoracoscopy achieves minimally invasive incisions, the extent of intrapleural decortication and lung tissue injury is comparable to that of traditional thoracotomy. When dense adhesions hinder pleural dissection, enlargement of the incision for open thoracotomy remains necessary. To ensure drainage, 1–2 thick drainage tubes are typically inserted postoperatively. However, compression of intercostal nerves by drainage tubes during lung re-expansion and patient movement often triggers breakthrough pain refractory to conventional PCIA combined with oral medications, necessitating opioid rescue analgesia. Given the paucity of research on postoperative analgesia for this disease, our team adopted a multimodal analgesia protocol using ropivacaine INB during chest closure, combined with PCIA and oral medications (17), yielding favorable clinical outcomes.

INB, a crucial technique in pain management, achieves effective analgesia by injecting local anesthetics around intercostal nerves or using physical interventions to disrupt the “pain-muscle spasm-ischemia-pain” cycle. Clinically widely used, it treats thoracolumbar painful conditions and serves as an essential component of combined anesthesia and postoperative analgesia for thoracoabdominal surgeries (lung, breast, rib, liver, kidney procedures, etc.) (18). Guided by ERAS (Enhanced Recovery After Surgery), INB in thoracic surgeries significantly alleviates pain, reduces complications, inhibits the stress response, and accelerates rehabilitation (19). Technically, ultrasound guidance has become the mainstream for INB, favored for real-time imaging, radiation-free operation, and flexibility (20). While ultrasound guidance offers real-time imaging, it often prolongs preoperative preparation. In contrast, naked-eye or thoracoscopic visualization shortens procedure time but presents technical challenges: post-dissection intercostal structures are obscured, requiring careful nerve identification for precise perineural injection. Pleural rupture during stripping risks drug leakage, undermining analgesic efficacy, so immediate injection site adjustment ensures intercostal tissue infiltration. Active puncture site bleeding is promptly controlled by compression or electrocoagulation (Figure 2). Clinically, this approach reduced analgesic use before anesthesia recovery and improved mobility, with patients transferring independently from the operating table to a stretcher post-awakening. Study data show no significant difference in postoperative drainage volume versus the conventional analgesia group, no reoperations or complications, and favorable follow-up outcomes.

In this study, significant baseline differences in operative time, intraoperative blood loss, and incision length—mainly due to variations in lesion extent and surgical complexity—were observed. Clinical observations showed that moderate-to-severe pain predominantly occurred from the morning after surgery until drainage tube removal, during which PCIA-induced adverse effects like nausea and vomiting often triggered muscle spasms, forming a “pain-drug side effects-discontinuation-increased pain vicious cycle (21). A multi-dimensional evaluation of different analgesic regimens was performed, assessing metrics such as the 24-hour post-surgery mean NRS score, peak NRS score, NRS score after tube removal, and rescue analgesic administration frequency. Results indicated that the multimodal analgesia combining ropivacaine INB, PCIA, and oral medications significantly outperformed the conventional regimen in the first 24 hours post-surgery and at the pain peak, with median NRS scores decreasing by 1 point, rescue analgesic administrations reducing by one instance, and the proportion of patients needing additional analgesics dropping by about 50%. However, no significant differences in pain scores were found between the two groups after tube removal, suggesting that postoperative pain was mainly caused by drainage-tube-induced intercostal nerve compression. Notably, despite ropivacaine’s short half-life of 5–6 hours, the significant reduction in NRS scores observed at 24 hours postoperatively likely reflects the synergistic effects of multimodal analgesia, where ropivacaine’s early analgesic effect was complemented by continuous PCIA and oral analgesics to maintain pain control. The limited duration of ropivacaine alone, combined with the gradual tapering of analgesic pump effects, may have contributed to the diminished group differences after tube removal (22). It should be emphasized that the NRS assessments in this study were limited to the early postoperative period up to drain removal, as this phase aligns with the key target of multimodal analgesia: addressing acute pain driven by drainage tube-induced intercostal nerve compression. Once the tube is removed, pain scores decrease significantly with no group differences, making this early period the critical window for evaluating the intervention’s efficacy. Furthermore, as no statistical differences were detected in drainage tube removal time, postoperative discharge time, and hospitalization costs, the multimodal analgesic approach was proven to enhance postoperative comfort and compliance without imposing extra financial or time burdens on patients.

This study has several limitations. First, the study population comprised patients with stage III tuberculous empyema from a single-center dataset, which may limit generalizability and external validity. Second, due to its retrospective design and small sample size, it was difficult to control for confounding factors. Variables such as intravenous analgesic pump activation frequency, pump discontinuation timing, surgeon-related expertise variability, and preoperative inflammatory marker fluctuations may have impacted outcomes. Future multicenter, randomized controlled trials are needed to validate analgesic efficacy and confirm these findings. Third, pain assessments were based on resting pain only, which may not fully reflect pain experiences during physical activity or dynamic clinical scenarios.

Conclusions

In conclusion, this study demonstrates that for patients with stage III tuberculous empyema undergoing surgery, a multimodal analgesic regimen combining ropivacaine-based INB, PCIA, and oral medications significantly improves postoperative analgesia. This approach reduces rescue analgesic use, minimizes adverse effects, and enhances patient compliance and satisfaction without increasing healthcare costs or delays in discharge.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1308/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1308/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1308/prf

Funding: This work was supported by the Shaanxi Province Key Research and Development Project (No. 2023-YBSF-336).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1308/coif). The 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 and its subsequent amendments. The study was approved by the Ethics Committee of Xi’an Chest Hospital (Approval R2023-004-01) and 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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