Lidocaine as a promising adjunct to reduce complications after lung resection

Introduction

Major lung resection remains a cornerstone in the treatment of pulmonary cancer. Despite the development of minimally invasive surgery techniques and implementation of enhanced recovery pathways, postoperative (pulmonary) complications occur to a clinically relevant extent and play a crucial role in postoperative morbidity and mortality (1). This is because lung resection induces a nonspecific systemic inflammatory response syndrome of varying intensity, which is associated with an increased risk of postoperative pulmonary complications (PPCs), often progressing to acute postoperative respiratory failure. Hypoxemia, surgical trauma and mechanical stress from invasive ventilation contribute, among other things, to the activation of innate immune cells, leukocyte activation and the release of reactive oxygen species, procoagulant factors, as well as proinflammatory mediators and cytokines. This inflammatory cascade often results in disruption of the alveolar-capillary barrier, leading to alveolar edema, an increased alveolo-arterial difference in partial oxygen pressure, ventilation-perfusion mismatch and leading to organ dysfunction. Complex ischemia-reperfusion-triggered mechanisms are believed to be major contributors to these effects. Similar to sepsis or cardiocirculatory insufficiency following vascular surgery, pulmonary vascular endothelial dysfunction and degradation of the endothelial glycocalyx play a pivotal role.

In recent years, attention has been directed toward strategies attenuating this inflammation cascade. There is some evidence suggesting that prehabilitation, the choice and settings of the ventilation mode, fluid management strategies, the extent of surgery (minimally invasive vs. open thoracotomy), and certain pharmacological approaches, such as the use of volatile anesthetics, particularly sevoflurane, may have beneficial effects. Among these approaches, the administration of lidocaine has emerged as a potentially therapeutic option. Lidocaine, primarily synthesized in 1948 as Xylocaine and used for providing analgesia since the 1950s, possesses not only well-known local anesthetic properties but also systemic anti-inflammatory, anti-hyperalgesic, and anti-arrhythmic effects (2). These properties have prompted investigation of perioperative lidocaine infusions in a variety of surgical specialties. However, evidence specific to thoracic surgery remains limited (3).

Summary

De la Gala et al. conducted a single-centre randomized controlled trial investigating the potential impact of lidocaine administered via intravenous and paravertebral infusion on perioperative inflammation following lung resection (4). The primary hypothesis was that lidocaine would (I) reduce peri- and postoperative inflammation, as assessed by markers such as interleukin-6 (IL-6) and tumor-necrosis-factor-alpha (TNF-α), and (II) consequently decrease the rate of postoperative (pulmonary) complications. Lidocaine infusion was compared with continuous infusion of remifentanil. A total of 154 patients undergoing lung resection via video-assisted thoracic surgery (VATS) were included. Exclusion criteria comprised, among others, conditions that might potentially influence the inflammatory response. There were three study groups: one receiving intravenous lidocaine (1.5 mg/kg/h), one receiving paravertebral lidocaine (2 mg/kg/h), and one receiving an intravenous remifentanil infusion (0.1 µg/kg/min). Maintenance of anesthesia was achieved through the administration of fentanyl and sevoflurane. At several peri- and postoperative time points, various cytokines, including IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP), and TNF-α, were measured both in blood samples and in broncho-alveolar lavage fluid. Postoperatively, all patients received a continuous paravertebral infusion of ropivacaine (0.2%) as well as morphine patient-controlled intravenous analgesia (PCIA). Participants who received lidocaine exhibited significantly lower serum cytokine levels as well as reduced cytokine concentrations in broncho-alveolar lavage from the postoperative dependent lung. Both the intravenous and paravertebral lidocaine groups showed fewer major postoperative complications [odds ratio (OR) 0.44]. PPCs were also less frequent in the lidocaine groups compared with the remifentanil group (22.3% vs. 45.1%; P=0.004). However, no significant effect could be observed on postoperative pain levels, length of hospital stay, or unplanned readmission. The authors concluded that lidocaine infusion, administered either intravenously or paravertebrally, may lead to fewer major (short-term) postoperative complications, possibly due to its immunomodulatory effects.

Interpretation and clinical implications

De la Gala et al. address a highly relevant and timely topic: the role of perioperative inflammation following thoracic surgery and the potential impact of perioperative lidocaine administration.

The concept of lidocaine exerting anti-inflammatory and immunomodulatory effects beyond its established role as a local anesthetic is not new (5). However, the successful translation of this concept into improved clinical outcomes in thoracic surgery has remained limited. Previous studies evaluating lidocaine in this context have primarily focused on postoperative pain, yielding inconsistent and overall inconclusive results. A recent meta-analysis by Mamun et al. provides a comprehensive overview of the current evidence (3).

In the present single-center randomized trial, the authors demonstrate that both paravertebral and intravenous administration of lidocaine significantly reduce the incidence of major postoperative complications (defined as Clavien-Dindo grade ≥3) from around 12% to 4%. In addition, significant attenuation of systemic and local inflammatory markers such as IL-6 measured in both plasma and bronchoalveolar lavage fluid was observed.

These findings are remarkable in several respects. First, few interventions in thoracic surgery have demonstrated such a pronounced reduction in PPCs. Given that PPCs are among the most frequent postoperative complications, their high incidence enhances the ability to detect potential effects. Second, the study supports the emerging concept that perioperative inflammation is not merely a bystander but a potential therapeutic target in the perioperative setting. In addition, there are further studies that were also able to demonstrate elevated systemic inflammatory markers following lung resection procedures. However, these analyses are methodologically rather heterogeneous, with strongly varying study designs (6-9).

Studies regarding the effects of lidocaine in this context are scarce and, so far, the exception. In this context, the study by Zhang et al. is also noteworthy (10). Investigating the effect of lidocaine on myocardial injury after non-cardiac surgery (MINS) in thoracic procedures, the authors similarly observed a reduction in systemic inflammatory markers, particularly IL-6. However, this did not translate into a reduction in the incidence of MINS, suggesting that modulation of inflammation alone may not be sufficient to influence myocardial outcomes in this patient population.

An especially intriguing aspect of the study is the absence of a clear difference between the routes of lidocaine administration. Traditionally, regional techniques, particularly paravertebral or neuraxial approaches, have been considered the so-called gold standard. The present findings challenge this paradigm, suggesting that intravenous administration of lidocaine, which is considerably simpler to implement, may achieve comparable effects to paravertebral infusion, thereby suggesting a potential avenue for comparison with the well-established epidural administration of local anesthetics. Alternatively, the high systemic absorption associated with paravertebral administration may result in a predominantly systemic mechanism of action.

Despite its strengths, the study has several important limitations. It is a single-center trial with a relatively small sample size, raising the possibility of an overestimation of treatment effects and susceptibility to random variation. Furthermore, the choice of a remifentanil-based anesthetic regimen as the sole comparator limits generalizability, as this does not reflect current best practice in all settings, particularly given the potential pro-nociceptive and possibly pro-inflammatory effects associated with the use of high-dose remifentanil. One could argue that the observed benefit is not solely attributable to lidocaine. It may reflect less favorable outcomes associated with remifentanil rather than a direct protective effect of lidocaine itself. Notably, the reported incidence of postoperative complications appears relatively high, particularly given the predominance of minimally invasive procedures. The use of sevoflurane should also be considered with caution, as volatile anesthetics have been shown to exert immunomodulatory and anti-inflammatory effects, which may have influenced the observed outcomes. It should also be considered that the proportion of conversion from VATS to thoracotomy was relatively higher in the group of remifentanil. The more extensive surgical resection and associated tissue trauma may have contributed to a more pronounced inflammatory response.

The observed reduction in inflammatory markers should be interpreted with appropriate caution. While these findings lend support to the biological plausibility of the intervention, they do not in themselves establish a causal relationship. It remains to be clarified whether the attenuation of cytokine levels reflects a direct therapeutic mechanism or is more closely associated with broader processes of clinical recovery. In this context, inflammatory markers may represent, at least in part, surrogate indicators rather than definitive mediators of the observed effects. Overall, although the magnitude of the reported effect appears encouraging, careful interpretation is warranted. These findings provide a valuable basis for further investigation but should be considered alongside the methodological characteristics of the study. Accordingly, clinical interest should be accompanied by continued emphasis on rigorous study design and confirmation in future trials.

Conclusions

The study by de la Gala et al. provides data suggesting that intraoperative lidocaine, whether administered intravenously or paravertebrally, may be associated with fewer postoperative complications and could attenuate inflammation after lung resection. These findings support a possible shift of paradigm from purely analgesic strategies toward perioperative modulation of inflammation as an additional therapeutic target within the framework of enhanced recovery after surgery (ERAS) pathways. However, adequately powered multi-center randomized trials are required to determine whether lidocaine can serve as a meaningful adjunct in this context.

Acknowledgments

This manuscript was prepared with the assistance of artificial intelligence (AI)-based tools solely for the purpose of improving language clarity and readability. No AI tools were used to generate, analyze, or interpret scientific content, data, or conclusions. All content remains the original work of the authors. The final text was carefully reviewed and verified by the authors to ensure accuracy, integrity, and compliance with the journal’s standards.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1153/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-2026-1153/coif). The authors have no conflicts of interest to declare.

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