术中利多卡因输注在胰腺癌行胰腺切除术患者中的应用：一项机制性、多中心随机临床试验。
Intraoperative lidocaine infusion in patients undergoing pancreatectomy for pancreatic cancer: a mechanistic, multicentre randomised clinical trial.
机构信息
Department of Anaesthesiology, Zhongshan Hospital, Shanghai, China; Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Anaesthesiology, Fudan University Shanghai Cancer Centre, Shanghai, China.
出版信息
Br J Anaesth. 2022 Aug;129(2):244-253. doi: 10.1016/j.bja.2022.03.031. Epub 2022 Jun 11.
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 h, after 1.5 mg kg 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.
背景
静脉内利多卡因通过抗炎作用、抗肿瘤作用或两者兼有，被认为可以改善胰腺癌手术后的长期生存。我们研究了术中利多卡因是否可以改善胰腺癌胰切除术的生存，并研究了利多卡因是否改变中性粒细胞胞外陷阱（NETs）的形成，NETs 水平升高与预后不良相关。
方法
接受胰切除术的患者被随机分配接受静脉内利多卡因（麻醉诱导时给予 1.5mg/kg 推注后，持续输注 2mg/kg/h）或生理盐水安慰剂。主要结局是术后 3 年的生存/无病生存率。次要结局（对治疗分配进行了屏蔽）包括术中阿片类药物（舒芬太尼）剂量、术后并发症以及循环和肿瘤相关 NETs（免疫荧光测定、酶联免疫测定或两者）。
结果
共有 563 名患者（女性占 34.6%；中位年龄为 64 岁）完成了 3 年的临床随访。总体而言，283 名患者接受利多卡因输注，280 名患者接受安慰剂。利多卡因输注并未改变总体生存率（危险比 [HR]=0.98；95%置信区间 [CI]，0.81-1.17；P=0.79）或无病生存率（HR=0.91；95%CI，0.71-1.17；P=0.44）。与安慰剂相比，利多卡因输注时术中舒芬太尼剂量降低（47.6μg[4.6]）（68.4μg[4.8]；P<0.001），但两组术后并发症和住院时间相似。术后 3 天内，循环 NETs 水平降低，但肿瘤相关 NETs 未因术中治疗而改变。
结论
在接受胰腺癌胰切除术的患者中，术中输注利多卡因不能提高总生存率或无病生存率。循环 NETs 的形成减少在胰腺肿瘤组织中不存在。
临床试验注册
NCT03245346；更新于 Chi-CTR-2000035469。
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