Lidocaine effects on neutrophil extracellular trapping and angiogenesis biomarkers in postoperative breast cancer patients with different anesthesia methods: a prospective, randomized trial

BMC Anesthesiol. 2024 Apr 27;24(1):162. doi: 10.1186/s12871-024-02540-7.

Abstract

Background: Anesthesia techniques and drug selection may influence tumor recurrence and metastasis. Neutrophil extracellular trapping (NETosis), an immunological process, has been linked to an increased susceptibility to metastasis in individuals with tumors. Furthermore, recurrence may be associated with vascular endothelial growth factor A (VEGF-A), a mediator of angiogenesis. This study investigates the impact of lidocaine (combined with sevoflurane or propofol anesthesia ) during breast cancer surgery inhibits the expression of biomarkers associated with metastasis and recurrence (specifically H3Cit, NE, MPO, MMP-9 and VEGF-A).

Methods: We randomly assigned 120 women undergoing primary or invasive breast tumor resection to receive one of four anesthetics: sevoflurane (S), sevoflurane plus i.v. lidocaine (SL), propofol (P), and propofol plus i.v. lidocaine (PL). Blood samples were collected before induction and 3 h after the operation. Biomarkers associated with NETosis (citrullinated histone H3 [H3Cit], myeloperoxidase [MPO], and neutrophil elastase [NE]) and angiogenesis were quantified using enzyme-linked immunosorbent assays.

Results: Patient and breast tumor characteristics, along with perioperative management, did not differ between study groups. In intra-group comparisons, S and P groups demonstrated a statistically significant increase in post-operative MPO (S group: 10.39[6.89-17.22] vs. 14.31[8.55-20.87] ng ml-1, P = 0.032; P group: 9.45[6.73-17.37] vs. 14.34[9.87-19.75] ng ml-1, P = 0.035)and NE(S group: 182.70[85.66-285.85] vs. 226.20[91.85-391.65] ng ml-1, P = 0.045; P group: 154.22[97.31-325.30] vs. 308.66[132.36-483.57] ng ml-1, P = 0.037) concentrations compared to pre-operative measurements, whereas SL and PL groups did not display a similar increase. H3Cit, MMP-9, and VEGF-A concentrations were not significantly influenced by the anesthesia techniques and drugs.

Conclusions: Regardless of the specific technique employed for general anesthesia, there was no increase in the postoperative serum concentrations of MPO and NE after perioperative lidocaine infusion compared to preoperative serum concentrations. This supports the hypothesis that intravenous lidocaine during cancer surgery aimed at achieving a cure may potentially decrease the likelihood of recurrence. Further interpretation and discussion of clinical implications are warranted, emphasizing the significance of these findings in the context of cancer surgery and recurrence prevention.

Clinical trial registration: ChiCTR2300068563.

Keywords: Angiogenesis; Breast cancer; Lidocaine; Neutrophil extracellular trapping; Propofol; Recurrence; Sevoflurane.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Local / administration & dosage
  • Angiogenesis
  • Biomarkers / blood
  • Breast Neoplasms* / surgery
  • Extracellular Traps / drug effects
  • Extracellular Traps / metabolism
  • Female
  • Humans
  • Lidocaine* / administration & dosage
  • Middle Aged
  • Neovascularization, Pathologic*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Propofol* / administration & dosage
  • Propofol* / pharmacology
  • Prospective Studies
  • Sevoflurane / administration & dosage
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Lidocaine
  • Propofol
  • Sevoflurane
  • Anesthetics, Local
  • Biomarkers
  • Anesthetics, Inhalation
  • Vascular Endothelial Growth Factor A