Thoracic paravertebral block with liposomal bupivacaine versus ropivacaine for postoperative analgesia in thoracic surgery: a randomized controlled study

Introduction

Surgical resection is the standard treatment for early-stage lung cancer. While the adoption of thoracoscopic techniques has substantially reduced surgical trauma compared to traditional thoracotomy, the incidence of moderate-to-severe postoperative pain remains as high as 62.7% (1). Inadequately managed acute postoperative pain not only delays recovery but may also contribute to complications such as respiratory infections, lower extremity deep vein thrombosis, and chronic pain (2,3). Opioid analgesics are commonly used for postoperative pain; however, adverse events including constipation, nausea, and vomiting may hinder recovery (4). Current guidelines recommend implementing a multimodal analgesic regimen that incorporates regional nerve blocks to improve pain control and reduce opioid consumption (5).

Thoracic paravertebral block (TPVB) is an established analgesic technique following thoracic surgery. The 2023 guidelines from the European Association for Thoracic Surgery and the European Society for Enhanced Recovery After Surgery endorse TPVB as a recommended modality for postoperative analgesia in thoracic procedures (6). However, conventional local anesthetics such as ropivacaine and bupivacaine typically provide analgesia for only 4–6 hours (7). Even with adjuvant agents, the analgesic duration is extended only to approximately 24 hours (7). This limited duration reduces the overall effectiveness of TPVB for postoperative pain management. Liposomal bupivacaine (LB), a sustained-release formulation of a local anesthetic, can provide analgesia for up to 72 hours (8). Nevertheless, evidence regarding the use of LB in TPVB remains limited (9). Therefore, we conducted this randomized controlled trial to evaluate the analgesic efficacy of TPVB with LB in 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-aw-2212/rc).

Methods

Study design and participants

This prospective, randomized controlled trial was conducted at Beijing Chest Hospital in China. The study protocol was approved by the Ethics Committee of Beijing Chest Hospital (No. 2024-22, Clinical Trial/Scientific Research Review), and written informed consent was obtained from all participants. The trial was registered with the Chinese Clinical Trial Registry (ChiCTR2400087560) on July 30, 2024, with the first patient enrolled in August 2024. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Eligible patients were: (I) aged 35 to 70 years; (II) had an American Society of Anesthesiologists (ASA) physical status of I to III; and (III) were scheduled for video-assisted thoracic surgery (VATS), including wedge resection, segmentectomy, or lobectomy. Exclusion criteria were as follows: (I) contraindications to TPVB (e.g., patient refusal, infection or tumor at the puncture site, coagulopathy); (II) history of major cardiovascular disease [including but not limited to myocardial infarction, angina, stroke, atrioventricular block, heart failure (New York Heart Association class III–IV), or severe valvular heart disease]; (III) preexisting chronic pain syndrome; (IV) preoperative hepatic or renal dysfunction; (V) inability to communicate or report pain; and (VI) voluntary withdrawal from the study. Patients requiring conversion to thoracotomy during the procedure were also excluded.

The number and location of surgical incisions for all patients were determined preoperatively by the surgeon. The specific surgical procedure was selected intraoperatively by the surgeon based on the pathological findings. The skin incision was about 3.5 cm long. In our hospital, all patients undergoing minimally invasive VATS routinely receive postoperative placement of a single 18-Fr chest tube. The placement of the chest tubes was determined by the surgeon and was located within the 4th to 6th intercostal spaces, according to the patient’s clinical requirements.

Randomisation and masking

Participants were randomly allocated in a 1:1 ratio to receive either liposomal bupivacaine (LB group) or ropivacaine (control group) using a simple randomization procedure. The allocation sequence was computer-generated based on a random number table via SPSS software (version 26.0). To enhance allocation concealment, the sequence entry for patient assignment began at a pre-specified point (the 10th entry), with odd numbers assigned to the LB group and even numbers to the control group.

Blinding was implemented using sequentially numbered, opaque, sealed envelopes. The group assignment for each participant was placed in an envelope by an independent researcher and delivered by a study nurse to the anesthesiologist performing the TPVB. This anesthesiologist was solely responsible for performing the TPVB and took no part in subsequent postoperative follow-up or data collection.

Owing to the distinct milky appearance of LB, the procedural anesthesiologist could not be blinded to group assignment. However, participants, anesthesiologist and all outcome assessors remained blinded to treatment allocation throughout the study. Randomization and allocation were managed entirely by an independent research team not involved in clinical care or outcome evaluation.

Anesthesia protocol

All enrolled patients received general anesthesia maintained with total intravenous anesthesia. For patients with an Apfel score greater than 2 (assigning 1 point each for female sex, history of postoperative nausea and vomiting, history of motion sickness, nonsmoker status, and postoperative opioid use), 4 mg of ondansetron hydrochloride was administered intravenously after anesthesia induction for nausea and vomiting prophylaxis. All patients received 4 mg of intravenous dexamethasone during surgery for additional antiemetic prophylaxis, along with oral acetaminophen (0.5 g per tablet) on the day of surgery.

Anesthesia was induced after 5 minutes of preoxygenation via face mask. The induction regimen consisted of sufentanil 0.3 µg/kg, midazolam 0.06 mg/kg, and target-controlled infusion (TCI) of propofol (2–4 µg/mL plasma concentration) and remifentanil (1–3 ng/mL plasma concentration). Following loss of consciousness, 0.6 mg/kg of rocuronium bromide was administered intravenously. A double-lumen endotracheal tube was placed under bronchoscopic guidance, with size selection based on the patient’s height, sex, and airway anatomical characteristics.

Mechanical ventilation was initiated with an oxygen flow rate of 3 L/min, a tidal volume of 6–8 mL/kg, a respiratory rate of 13 breaths per minute, and an inspiration-to-expiration ratio of 1:1.5. End-tidal CO₂ was maintained between 30 and 40 mmHg. Anesthesia was maintained using TCI of propofol at 2–4 µg/mL (plasma concentration) and remifentanil at 1–3 ng/mL (plasma concentration). Bispectral index (BIS) was monitored and maintained between 40 and 60. Vasopressors were administered as needed to maintain mean arterial pressure (MAP) within 20% of baseline values (Baseline hemodynamic values were established by calculating the average of three blood pressure readings taken immediately upon the patient’s arrival in the preoperative preparation room) in both the preoperative preparation room and the operating room, and their use was recorded. Supplemental boluses of sufentanil (5–10 µg) and rocuronium were administered intraoperatively according to clinical requirements.

Analgesic measures

All patients received patient-controlled intravenous analgesia postoperatively. The analgesic solution contained sufentanil (2 µg/kg, calculated based on patient body weight), flurbiprofen axetil (200 mg), and normal saline, diluted to a total volume of 100 mL. The patient-controlled analgesia (PCA) pump was programmed to deliver a continuous background infusion at 2 mL/h, with a bolus dose of 2 mL and a lockout interval of 15 minutes. All patients received instruction on the use of the PCA device. A rescue analgesia protocol was established: if pain was inadequately controlled by the PCA regimen, 30 mg of ketorolac tromethamine was administered intramuscularly. If pain persisted, a subsequent intramuscular injection of 10 mg morphine was administered.

The TPVB was performed preoperatively by an experienced anesthesiologist. After establishing peripheral venous access in the preoperative preparation room, standard monitoring was applied, including electrocardiography, invasive arterial pressure monitoring, and pulse oximetry. Under ultrasound guidance (Wisonic Labat SP, China), the block was performed with the patient in the lateral decubitus position, surgical side up. Following skin disinfection, a linear high-frequency probe was positioned approximately 2.5 cm lateral to the spinous process at the target levels to identify the thoracic paravertebral space (Figure S1). Subcutaneous local infiltration with 2 mL of 0.2% lidocaine hydrochloride was administered at the T4–T5 and T6–T7 intercostal levels. A 100 mm nerve stimulation needle (NanoLine nerve stimulation block needle, Facet, 21 G) was then advanced using an out-of-plane technique under real-time ultrasound guidance, with intermittent injection of 1–2 mL of normal saline to confirm needle tip placement and hydrodissection of the tissue plane. Correct needle position was confirmed by visualization of a hypoechoic fluid collection compressing the pleura (the subpleural hydrodissection sign). All patients received a dual-level block at T4–T5 and T6–T7. In the LB group, 133 mg/15 mL of LB (10 mL LB + 5 mL saline) was injected at each level. In the control group, 15 mL of 0.5% ropivacaine (75 mg) was injected at each level.

Outcomes

The primary endpoint was the numerical rating scale (NRS) score for pain during coughing at 24 hours after surgery. Secondary efficacy endpoints included: (I) resting and cough NRS scores at 4 hours postoperatively; (II) resting and activity NRS scores at 24 hours postoperatively; (III) resting, activity, and cough NRS scores at 48 and 72 hours postoperatively; (IV) total opioid consumption at intraoperatively and at 24 and 48 hours postoperatively; and (V) the Quality of Recovery-15 (QoR-15) score at 48 hours postoperatively. Safety endpoints comprised: (I) vital signs including heart rate, MAP, and oxygen saturation measured preoperatively, at 0.5, 1, and 2 hours during surgery, at extubation, and at 4, 24, and 48 hours after surgery; and (II) adverse events occurring postoperatively during hospitalization.

The QoR-15 is a validated patient-reported outcome measure that comprehensively evaluates postoperative recovery quality. This instrument has been recommended as a standard assessment tool in perioperative clinical trials. For the QoR-15, a minimal clinically important difference (MCID) of 8.0 points is considered clinically significant (10).

Total opioid consumption was assessed by calculating the cumulative amount of intravenous opioids administered during the intraoperative and postoperative periods, including those delivered via PCA and rescue analgesia, along with any additional oral opioids voluntarily taken by the patient. These values were then converted to parenteral morphine milligram equivalents (MME) for analysis.

Statistical analysis

Based on our preliminary study, the mean ± standard deviation (SD) for the 24-hour cough NRS score was 2.9±1.2 with LB and 3.8±1.4 with ropivacaine. With a two-sided α of 0.05 and 90% power (β=0.1), a sample size of 92 patients was calculated. Accounting for a 10% dropout rate, a total of 100 patients were planned for enrollment, with 50 patients assigned to each group.

All statistical analyses were performed using SPSS software (version 26.0). Data are presented according to their distribution. Normally distributed continuous variables are expressed as mean ± SD and were compared between groups using the independent samples t-test. Non-normally distributed continuous data are expressed as median [interquartile range (IQR)] and were compared using the Mann-Whitney U test. Categorical data are presented as numbers (proportions) and were compared between groups using the chi-squared test or Fisher’s exact test. A two-sided P value <0.05 was considered statistically significant.

Results

Baseline demographics

From August 2024 to December 2024, 206 patients were assessed for eligibility, and 109 patients were randomized preoperatively. Nine patients were excluded due to conversion to thoracotomy during surgery. Ultimately, 100 patients were included in the final analysis (LB group, n=50; ropivacaine group, n=50; Figure 1). No statistically significant differences were observed between the two groups in age, height, weight, body mass index, sex, ASA physical status classification, surgical characteristics, or preoperative comorbidities (all P>0.05; Table 1).

Figure 1 Trial profile. PCA, patient-controlled intravenous analgesia.

Postoperative pain management and analgesic requirements

As shown in Table 2 and Figure S2, the NRS pain score during coughing at 24 hours postoperatively was significantly lower in the LB group than in the control group (P=0.001). Additionally, pain scores at rest, during activity (slow walking), and during coughing were significantly lower in the LB group compared to the control group at both 24 and 48 hours postoperatively. However, a statistically significant difference between groups was observed only during coughing at 72 hours postoperatively. No between-group differences were found in NRS pain scores at 4 hours postoperatively, or in resting and activity pain scores at 72 hours postoperatively. Furthermore, no significant differences were observed between the groups in rescue analgesia requirements within 24 and 48 hours postoperatively, or in MME at any time point during the first 48 hours after surgery.

Vasopressor use and perioperative recovery outcomes

No statistically significant differences were observed in heart rate, MAP, or oxygen saturation between the two groups at any time point during the perioperative period (P>0.05; Figure S3). During surgery, fewer patients in the LB group required dopamine compared to the control group (P=0.01). No statistically significant differences were found between groups in the duration of postoperative chest tube placement (P>0.05) or the duration of hospital stay (P>0.05). At 48 hours postoperatively, the LB group demonstrated significantly higher QoR-15 scores than the control group (P=0.03; Table 3).

Postoperative adverse events

The LB group showed significantly lower incidences of postoperative dizziness (14% vs. 36%, P=0.02) and vomiting (4% vs. 26%, P=0.004) during hospitalization compared to the control group (Table 4). However, no statistically significant differences were observed between the groups in the incidence of postoperative nausea, fever, shortness of breath, limb edema, or injection site pain (all P>0.05).

Discussion

In this randomized controlled trial, TPVB with LB demonstrated superior efficacy in managing acute postoperative pain following VATS compared to ropivacaine. Patients receiving LB exhibited significantly lower pain scores during the first 48 hours postoperatively. The LB group also required significantly less intraoperative dopamine and experienced lower incidences of postoperative vomiting and dizziness.

LB was selected for preoperative TPVB due to its unique extended-release pharmacokinetic profile. Its prolonged analgesic effect results from the sustained release of bupivacaine from multivesicular liposomes (8,11). This release follows a characteristic triphasic pattern (12), which produces a delayed onset of analgesia, typically occurring within 2 hours after administration. This pharmacokinetic property is particularly advantageous for postoperative pain management, as the onset of analgesia coincides with the resolution of intraoperative anesthetic and short-acting opioid effects, enabling a smooth transition during the early recovery period. This rationale is supported by findings from a crossover trial conducted by Zadrazil et al. (13).

Our analysis revealed that patients in the LB group exhibited lower NRS pain scores at rest, during activity, and during coughing within the first 48 hours postoperatively compared to the control group. The analgesic superiority of LB persisted through the third postoperative day, as demonstrated by significantly lower cough NRS scores. Consistent with improved analgesia, the LB group also demonstrated reduced demand for PCA bolus attempts on the first postoperative day. These findings indicate a prolonged postoperative analgesic effect with LB, which aligns with the results of a retrospective study by NeMoyer et al. That study evaluated patients receiving TPVB after both thoracoscopic and open thoracic procedures and concluded that LB effectively mitigated postoperative pain (14). In contrast to these promising results with TPVB, numerous studies investigating LB for post-thoracotomy analgesia via other techniques, such as local infiltration (15), intercostal nerve block (ICNB) (16), and combined pectoralis type II with serratus anterior plane block (PECS II-SAPB) (17), have reported unsatisfactory outcomes. We hypothesize that the superior efficacy of LB in TPVB may be attributed to the broader and more anatomically comprehensive sensory blockade achieved with this approach compared to alternative techniques. Additionally, TPVB produces unilateral sympathetic blockade, which may attenuate the intraoperative stress response and reduce postoperative inflammatory pain. The specific anatomical configuration of the paravertebral space, combined with the vesicular encapsulation that limits circumferential diffusion of LB and concentrates the drug predominantly at the injection site, likely contributes to its enhanced efficacy in this specific regional anesthesia technique.

Despite demonstrating superior analgesia, our study found no significant reduction in opioid consumption with LB. It is noteworthy that the calculated MME values in our study were higher than those reported in one previous study (18) but substantially lower than those reported in another study employing PCA alone (19). This may be attributed to the specific PCA protocol implemented in our trial. We consider the inclusion of a low background infusion a rational and necessary component to enhance central analgesia. Furthermore, regarding the difference between the groups, our findings are consistent with the conclusions of most existing studies, including the report by Dominguez et al., in which the LB group showed no decrease in opioid consumption within 24 hours postoperatively (20). Similarly, Weksler et al. (21) observed no reduction in opioid use when LB was administered via local incisional infiltration combined with ICNB. We speculate that although LB provides improved background analgesia for incisional pain, breakthrough pain from other sources, such as irritation of the diaphragm or parietal pleura by the chest tube, may still necessitate rescue opioids. This explanation aligns with patient reports of well-controlled incisional pain but occasional discomfort in areas such as the shoulder or costal margin. As the analgesic coverage of TPVB is anatomically finite (22), chest tube movement beyond the anesthetized dermatomes may elicit pain that requires supplemental opioid administration.

A notable finding in this study was the significantly reduced intraoperative vasopressor requirement in the LB group compared to the control group. We hypothesize that this difference may be attributed to the relatively weaker vasodilatory effect of LB relative to ropivacaine. This differential hemodynamic effect arises from ropivacaine’s higher affinity for vascular smooth muscle potassium channels (23), whereas the sustained-release profile of LB minimizes peak plasma concentrations that typically induce mild vasodilation (12). The hemodynamic stability associated with LB may be particularly advantageous for high-risk patients, such as the elderly or those with a history of myocardial infarction or cerebrovascular disease, by maintaining a more stable intraoperative blood pressure.

The QoR-15 score, a comprehensive patient-reported outcome measure (10), was significantly higher in the LB group at 48 hours postoperatively. Although the between-group difference did not reach the MCID threshold of 8.0 points, this trend suggests a potential benefit for postoperative recovery associated with LB. No significant difference in length of hospital stay was observed between the two groups in our study. The duration of hospitalization is typically determined by multiple factors, including the time to chest tube removal, the patient’s postoperative recovery progress, and the occurrence of postoperative complications. Consistent with our findings, studies evaluating LB, whether administered via TPVB (18), serratus anterior plane block (24), or ICNB (25), have not demonstrated a shorter hospital stay in the LB group. We speculate that the ability of LB to accelerate postoperative recovery may be limited.

It is noteworthy that the incidences of postoperative dizziness and vomiting were significantly lower in the LB group compared to the control group in our study. No postoperative pulmonary infections or thromboembolic events were observed in our study. All adverse events and complications were recorded based on entries in the medical record system.

There are several limitations in this study. First, it was conducted at a single center. While the findings reflect real-world clinical experience from our institution, future multi-center studies encompassing broader geographic regions are warranted to validate these results. Second, the extent of the sensory block was not assessed postoperatively. This omission prevented dynamic observation of the regression of sensory blockade over time and limited our ability to accurately manage pain originating from the distal end of the chest tube. Third, the assessment of preoperative anxiety and depression in patients was based solely on medical records, without the use of corresponding diagnostic scales. This may have led to an underestimation of the incidence of these conditions, particularly anxiety. Fourth, we did not perform continuous QoR-15 follow-up postoperatively. Therefore, our findings only suggest the potential of LB to facilitate postoperative recovery. Serial postoperative assessments would be necessary to obtain more detailed and comprehensive dynamic recovery profiles. These limitations highlight the need for further investigation to address these gaps and provide a more comprehensive evaluation of the LB treatment regimen.

Conclusions

In conclusion, this prospective randomized controlled trial demonstrates that LB, when administered via TPVB in patients undergoing thoracic surgery, provides superior acute postoperative analgesia and reduces the incidence of postoperative dizziness and vomiting compared to ropivacaine. As a component of a multimodal analgesic regimen, although LB did not reduce opioid consumption, it improved acute postoperative pain. Further large-scale, multicenter trials are warranted to confirm the clinical utility of LB for paravertebral analgesia.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CONSORT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2212/rc

Trial Protocol: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2212/tp

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2212/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2212/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-aw-2212/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Beijing Chest Hospital (No. 2024-22, Clinical Trial/Scientific Research Review). Written informed consent was obtained from all participants.

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/.

References

1. Liu Y, Xiao S, Yang H, et al. Postoperative pain-related outcomes and perioperative pain management in China: a population-based study. Lancet Reg Health West Pac 2023;39:100822.
2. Thomas MA. Pain management - the challenge. Ochsner J 2003;5:15-21.
3. Perkins FM, Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology 2000;93:1123-33.
4. Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol 2012;13:e58-68.
5. Clinical Practice Guidelines for Enhanced Recovery Surgery in China. Chinese Journal of Anesthesiology 2021;41:1028-34.
6. Batchelor TJP, Rasburn NJ, Abdelnour-Berchtold E, et al. Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS®) Society and the European Society of Thoracic Surgeons (ESTS). Eur J Cardiothorac Surg 2019;55:91-115.
7. Vorobeichik L, Brull R, Abdallah FW. Evidence basis for using perineural dexmedetomidine to enhance the quality of brachial plexus nerve blocks: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth 2017;118:167-81.
8. Viscusi ER. Liposomal drug delivery for postoperative pain management. Reg Anesth Pain Med 2005;30:491-6.
9. Gong R, Tan G, Huang Y. The Efficacy of Liposomal Bupivacaine in Thoracic Surgery: A Systematic Review and Meta-Analysis. J Pain Res 2024;17:4039-51.
10. Kleif J, Waage J, Christensen KB, et al. Systematic review of the QoR-15 score, a patient- reported outcome measure measuring quality of recovery after surgery and anaesthesia. Br J Anaesth 2018;120:28-36.
11. Grant GJ, Bansinath M. Liposomal delivery systems for local anesthetics. Reg Anesth Pain Med 2001;26:61-3.
12. Manna S, Wu Y, Wang Y, et al. Probing the mechanism of bupivacaine drug release from multivesicular liposomes. J Control Release 2019;294:279-87.
13. Zadrazil M, Marhofer P, Opfermann P, et al. Liposomal Bupivacaine for Peripheral Nerve Blockade: A Randomized, Controlled, Crossover, Triple-blinded Pharmacodynamic Study in Volunteers. Anesthesiology 2024;141:24-31.
14. NeMoyer RE. Paravertebral Nerve Block With Liposomal Bupivacaine for Pain Control Following Video-Assisted Thoracoscopic Surgery and Thoracotomy. J Surg Res 2020;246:19-25.
15. Thuppal S, Sleiman A, Chawla K, et al. Randomized Trial of Bupivacaine Versus Liposomal Bupivacaine in Minimally Invasive Lobectomy. Ann Thorac Surg 2022;114:1128-34.
16. Pedoto A, Noel J, Park BJ, et al. Liposomal Bupivacaine Versus Bupivacaine Hydrochloride for Intercostal Nerve Blockade in Minimally Invasive Thoracic Surgery. J Cardiothorac Vasc Anesth 2021;35:1393-8.
17. Marciniak D, Raymond D, Alfirevic A, et al. Combined pectoralis and serratus anterior plane blocks with or without liposomal bupivacaine for minimally invasive thoracic surgery: A randomized clinical trial. J Clin Anesth 2024;97:111550.
18. Yang Z, Liu M, Wang C, et al. Thoracic Paravertebral Block with Liposomal Bupivacaine Versus Plain Bupivacaine in Patients Undergoing Thoracoscopic Lung Resection: A Randomized Controlled Study. Drug Des Devel Ther 2025;19:6955-64.
19. Yan G, Chen J, Yang G, et al. Effects of patient-controlled analgesia with hydromorphone or sufentanil on postoperative pulmonary complications in patients undergoing thoracic surgery: a quasi-experimental study. BMC Anesthesiol 2018;18:192.
20. Dominguez DA, Ely S, Bach C, et al. Impact of intercostal nerve blocks using liposomal versus standard bupivacaine on length of stay in minimally invasive thoracic surgery patients. J Thorac Dis 2018;10:6873-9.
21. Weksler B, Sullivan JL, Schumacher LY. Randomized trial of bupivacaine with epinephrine versus bupivacaine liposome suspension in patients undergoing minimally invasive lung resection. J Thorac Cardiovasc Surg 2021;161:1652-61.
22. Marhofer D, Marhofer P, Kettner SC, et al. Magnetic resonance imaging analysis of the spread of local anesthetic solution after ultrasound-guided lateral thoracic paravertebral blockade: a volunteer study. Anesthesiology 2013;118:1106-12.
23. Kiper AK, Bedoya M, Stalke S, et al. Identification of a critical binding site for local anaesthetics in the side pockets of K(v) 1 channels. Br J Pharmacol 2021;178:3034-48.
24. Zhang M, Zheng Z, Xie X, et al. Comparison of continuous Serratus Anterior Plane Block (cSAPB) with bupivacaine versus single liposomal bupivacaine block in postoperative analgesia after Video-Assisted Thoracoscopic Surgery (VATS): a randomized controlled trial. BMC Anesthesiol 2025;25:399.
25. Xie L, Xi Y, He X, et al. Liposomal Bupivacaine vs. Plain Bupivacaine with Dexamethasone for Rhomboid Intercostal Block in the Management of Postoperative Pain After Video-Assisted Thoracoscopic Surgery: A Randomized Non-inferiority Trial. Pain Ther 2025;14:1513-30.