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

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.