Journal
BRITISH JOURNAL OF ANAESTHESIA
Volume 129, Issue 2, Pages 244-253Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.bja.2022.03.031
Keywords
disease-free survival; lidocaine; neutrophil extracellular traps; overall survival; pancreatic cancer
Categories
Funding
- National Natural Science Foundation of China [82102253, 81871591, 8211101501]
- Clinical Research Plan of SHDC [SHDC2020CR4064]
- Shanghai Municipal 2021 'Science and Technology Innovation Action Plan' [21JC1401400, 21S31902600]
- Natural Science Foundation of Shanghai [21ZR1413400]
- Shanghai Sailing Program [21YF1406800]
- 2019 Fudan University Zhuo-Xue Project [JIF159607]
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Intraoperative infusion of lidocaine did not improve overall or disease-free survival in patients undergoing pancreatectomy for pancreatic cancer. However, it reduced the use of intraoperative opioids and circulating NETs formation after surgery, but had no effect on tumor-associated NETs.
Background: Intravenous lidocaine has been postulated to improve long-term survival after surgery for pancreatic cancer through anti-inflammatory effects, anti-tumour effects, or both. We investigated whether intraoperative lidocaine improves survival after pancreatectomy for pancreatic cancer and whether lidocaine modified the formation of neutrophil extracellular traps (NETs), high levels of which are associated with poor prognosis. Methods: Patients undergoing pancreatectomy were randomly assigned to i.v. lidocaine (continuous intraoperative infusion of 2mg kg(-1) h(-1), after 1.5 mg kg(-1) bolus at induction of anaesthesia) or saline placebo. The co-primary outcomes were survival/disease-free survival 3 yr after surgery. Secondary outcomes (masked to treatment allocation) included intraoperative opioid (sufentanil) dose, postoperative complications, and circulating and tumour-associated NETs (immunofluorescence assay, enzyme-linked immune assay, or both). Results: A total of 563 participants (34.6% female; median age, 64 yr) completed 3 yr of clinical follow-up. Overall, 283 participants were randomised to lidocaine infusion, and 280 participants were randomised to placebo. Infusion of lidocaine did not alter overall (hazard ratio [HR]=0.98; 95% confidence interval [CI], 0.81-1.17; P=0.79) or disease-free survival (HR=0.91; 95% CI, 0.71e1.17; P=0.44). Mean intraoperative sufentanil dose was reduced by lidocaine infusion (47.6 mg [4.6]) compared with placebo (68.4 mg [4.8]; P<0.001), but postoperative complications and length of hospital stay were similar between groups. Circulating NETs were lower after lidocaine infusion up to 3 days after surgery, but tumour-associated NETs were not altered by intraoperative treatment. Conclusion: In patients undergoing pancreatectomy for pancreatic cancer, intraoperative infusion of lidocaine did not improve overall or disease-free survival. Reduced formation of circulating NETs was absent in pancreatic tumour tissue.
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