Effect of Intravenous Lidocaine on Serum Interleukin-17 After Video-Assisted Thoracic Surgery for Non-Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Purpose: Surgical stress promotes tumor metastasis. Interleukin (IL)-17 plays a pivotal role in cancer progression, and high IL-17 expression predicts poor prognosis of non-small-cell lung cancer (NSCLC). Lidocaine may exert tumor-inhibiting effects. We hypothesize that intravenous lidocaine attenuates surgical stress and reduces serum IL-17 levels during video-assisted thoracic surgery (VATS) for NSCLC.

Methods: This randomized, double-blind, placebo-controlled trial included 60 early-stage NSCLC patients undergoing VATS, into a lidocaine group (n = 30; intravenous lidocaine bolus 1.0 mg/kg, and 1.0 mg/kg/h until the end of surgery) or a normal saline control group (n = 30). The primary outcome was serum IL-17 level at 24 hours postoperatively. The secondary outcomes included serum IL-17 level at the time of post-anesthesia care unit (PACU) discharge, serum cortisol level at PACU discharge and postoperative 24 hours, pain scores (0-10) from PACU discharge to 48 hours postoperatively, incidences of postoperative nausea and vomiting, dizziness, and arrhythmia during 0-48 hours postoperatively, and 30-day mortality. Long-term outcomes included chemotherapy, cancer recurrence, and mortality.

Results: The lidocaine group had lower serum IL-17 at 24 hours postoperatively compared with the control group (23.0 ± 5.8 pg/mL vs 27.3 ± 8.2 pg/mL, difference [95% CI] = -4.3 [-8.4 to -0.2] pg/mL; P = 0.038). The lidocaine group also had reduced serum IL-17 (difference [95% CI] = -4.6 [-8.7 to -0.5] pg/mL), serum cortisol (difference [95% CI] = -37 [-73 to -2] ng/mL), and pain scores (difference [95% CI] = -0.7 [-1.3 to -0.1] points) at PACU discharge. During a median follow-up of 10 (IQR, 9-13) months, 2 patients in the lidocaine group and 6 patients in the control group received chemotherapy, one patient in the control group had cancer recurrence, and no death event occurred.

Conclusion: Intravenous lidocaine was associated with reduced serum IL-17 and cortisol following VATS procedures in early-stage NSCLC patients.

Trial registration: ChiCTR2000030629.

Keywords: interleukin-17; lidocaine; non-small-cell lung cancer; surgical stress; video-assisted thoracic surgery.

Conflict of interest statement

The authors reported no conflicts of interest for this work and declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

© 2021 Hou et al.

Figures

Figure 1

CONSORT flow diagram.

Figure 2

Perioperative heart rate and mean arterial pressure. (A) Heart rate. (B) Mean arterial pressure. Data are mean ± standard deviation. Green arrow indicates the infusion period of the study medication. P values between the lidocaine and control groups are shown.

Figure 3

Serum levels of IL-17 and cortisol. (A) Serum IL-17. (B) Serum cortisol. *P < 0.05, **P < 0.01 vs the baseline value. P values between the lidocaine and control groups are shown. Data are median (line within the box), interquartile range (box), and 5th–95th percentile values (whiskers).

Figure 4

Subgroup analysis. Subgroup analysis investigating the effect of intravenous lidocaine on serum IL-17 levels at postoperative 24 hours, according to age (≤ 50 y vs > 50 y), sex (female vs male), and cancer stage (T1-2 vs Tis).