Perioperative lidocaine and dexmedetomidine intravenous infusion reduce the serum levels of NETs and biomarkers of tumor metastasis in lung cancer patients: A prospective, single-center, double-blinded, randomized clinical trial

Baiqing Ren; Muqiao Cheng; Chao Liu; Huiwen Zheng; Jingyue Zhang; Wei Chen; Jie Song; Jingwen Zhuang; Tianya Liu; Rui Wang; Zhiping Wang

doi:10.3389/fonc.2023.1101449

Perioperative lidocaine and dexmedetomidine intravenous infusion reduce the serum levels of NETs and biomarkers of tumor metastasis in lung cancer patients: A prospective, single-center, double-blinded, randomized clinical trial

Front Oncol. 2023 Feb 24:13:1101449. doi: 10.3389/fonc.2023.1101449. eCollection 2023.

Authors

Baiqing Ren^{1

2}, Muqiao Cheng³, Chao Liu^{1

2}, Huiwen Zheng^{1

2}, Jingyue Zhang^{1

2}, Wei Chen^{1

2}, Jie Song^{1

2}, Jingwen Zhuang⁴, Tianya Liu^{1

2}, Rui Wang^{1

2}, Zhiping Wang^{1

2}

Affiliations

¹ Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
² Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
³ Department of Anesthesiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Department of Anesthesiology, The First People's Hospital of Changde City, Changde, China.

Abstract

Background: Neutrophil extracellular traps (NETs) can enhance the metastasis of non-small cell lung cancer (NSCLC). As biomarkers of tumor metastasis, metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) together with NETs are essential to endothelial-to-mesenchymal transition (EMT). We hypothesized that intravenous infusion of lidocaine and dexmedetomidine could reduce the production of NETs and biomarkers of tumor metastasis after video-assisted thoracic surgery (VATS) in NSCLC patients.

Method: The trial included 132 NSCLC patients undergoing VATS. The patients were equally randomized to a placebo group (Group C), a lidocaine group (Group L, intravenous lidocaine 8 mg/kg/h for 15 minutes before anesthesia, 2 mg/kg/h during surgery, and 1 mg/kg/h until 24 hours after surgery), a dexmedetomidine group (Group D, intravenous dexmedetomidine 2 μg/kg/h for 15 minutes before anesthesia, 0.5 μg/kg/h during surgery, and 0.25 μg/kg/h until 24 hours after surgery), and a dexmedetomidine plus lidocaine group (Group LD, combination use of lidocaine and dexmedetomidine). The primary outcome was the production of myeloperoxidase (MPO) and citrullinated histone-3 (H3Cit), biomarkers of NETs, on postoperative day (POD) 1. MMP-3, MMP-9, and VEGF-α, as biomarkers of tumor metastasis, were also evaluated on POD 1.

Results: The baseline patient characteristics and perioperative data did not differ between the study groups. MPO was significantly decreased in Groups L, D, and LD (-197.08 ± 34.01, -137.37 ± 32.41, and -189.45 ± 33.73 U/ml, P<0.001, respectively) compared with Group C (-106.51 ± 25.44 U/ml). H3Cit was also lessened in Groups L, D, and LD (-49.51 ± 9.11, -34.80 ± 10.37, and -51.82 ± 8.98 ng/ml, P<0.001, respectively) compared with Group C (-24.73 ± 7.65 ng/ml). Lidocaine and dexmedetomidine also reduced MMP-3 (-69.08 ± 13.22, -52.84 ± 13.78, -85.34 ± 12.59 vs. -40.55 ± 10.71 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), MMP-9 (-8.46 ± 1.68, -6.07 ± 1.82, -9.67 ± 1.43 vs. -4.28 ± 1.29 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), and VEGF-α (-95.55 ± 22.53, -71.65 ± 18.77, -104.89 ± 15.49 vs. -51.73 ± 16.27 pg/ml in Group L, D, LD vs. Group C, P<0.001, respectively) on POD 1.

Conclusion: In NSCLC patients, continuous perioperative intravenous infusion of lidocaine and dexmedetomidine significantly reduced the production of NETs and tumor metastasis biomarkers on POD 1. Meanwhile, it also decreased inflammation, protected cellular immune function, reduced pain and opioid consumption, and improved the quality of postoperative recovery.

Clinical trial registration: chictr.org.cn, identifier: 187049.

Keywords: dexmedetomidine; lidocaine; lung cancer; metastasis; neutrophil extracellular traps; tumor.

Grants and funding

This study was supported by 1. National Natural Science Foundation of China, 82270059; 2. Jiangsu Provincial Health Commission Medical Research Key Project, K2019003; 3. Jiangsu Natural Science Foundation, BK20221222; China Primary Health Care Foundation, YLGX-MZ-2022004; 4. The foundation of Xuzhou Science and Technology Department, KC21154.