TY - JOUR
T1 - Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer
T2 - a mechanistic, multicentre randomised clinical trial
AU - Zhang, Hao
AU - Qu, Mengdi
AU - Guo, Kefang
AU - Wang, Yanghanzhao
AU - Gu, Jiahui
AU - Wu, Han
AU - Zhu, Xuqin
AU - Sun, Zhirong
AU - Cata, Juan P.
AU - Chen, Wankun
AU - Miao, Changhong
N1 - Publisher Copyright:
© 2022 British Journal of Anaesthesia
PY - 2022/8
Y1 - 2022/8
N2 - 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 2 mg 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, 0.71–1.17; P=0.44). Mean intraoperative sufentanil dose was reduced by lidocaine infusion (47.6 μg [4.6]) compared with placebo (68.4 μg [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. Clinical trial registration: NCT03245346; updated in Chi-CTR-2000035469.
AB - 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 2 mg 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, 0.71–1.17; P=0.44). Mean intraoperative sufentanil dose was reduced by lidocaine infusion (47.6 μg [4.6]) compared with placebo (68.4 μg [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. Clinical trial registration: NCT03245346; updated in Chi-CTR-2000035469.
KW - disease-free survival
KW - lidocaine
KW - neutrophil extracellular traps
KW - overall survival
KW - pancreatic cancer
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U2 - 10.1016/j.bja.2022.03.031
DO - 10.1016/j.bja.2022.03.031
M3 - Article
C2 - 35697547
AN - SCOPUS:85131785326
SN - 0007-0912
VL - 129
SP - 244
EP - 253
JO - British journal of anaesthesia
JF - British journal of anaesthesia
IS - 2
ER -