■局部麻醉药因其镇痛和麻醉特性在围手术期被广泛使用,包括切除恶性肿瘤的外科手术。同时,化疗药物仍然是癌症治疗的基石,靶向快速分裂的癌细胞以抑制肿瘤生长。这两种药物之间的潜在相互作用引起了越来越多的关注,并且在肿瘤外科背景下可以考虑它们的联合使用。这篇综述探讨了关于局部麻醉药和化疗药物之间相互作用的现有证据。包括生物学机制和临床意义。
■根据系统评价和荟萃分析(PRISMA)指南的首选报告项目对电子数据库进行系统检索。选择标准被设计为在体外捕获,在体内,和临床研究评估局部麻醉剂和多种化疗药物之间的相互作用。筛选和数据提取由两名评审员独立进行。由于纳入研究的预期异质性,因此使用叙事方法对数据进行了综合。
■初步搜索产生了1225篇相关文章进行筛选,其中43人符合纳入标准。局部麻醉剂和化疗药物之间的相互作用是多方面的。体外研究经常表明,当这些药物联合使用时,细胞毒性谱发生了变化。与变化取决于具体的药物组合和癌细胞类型。机械上,一些相互作用归因于外排泵活性的改变,肿瘤抑制基因表达,或与肿瘤促进相关的细胞信号传导途径的改变。绝大多数体外研究报告了局部麻醉剂在增强化学治疗剂的抗肿瘤活性方面的潜在有益作用。在动物模型中,局部麻醉剂和化疗药物的联合给药对肿瘤生长显示出很大的有益作用,转移,和总体生存率。值得注意的是,目前尚未有任何临床研究报道局部麻醉药和化疗对癌症结局的可能相互作用.
■据报道,局部麻醉药和化学治疗剂之间的临床前相互作用是复杂的,并且包括一系列影响,虽然不是统一的,添加剂或协同。由于缺乏前瞻性试验,这些相互作用的临床意义仍不清楚。尽管如此,局部麻醉剂对化疗效果的调节值得在癌症手术中进行进一步的临床研究,在这些手术中它们可以一起使用。
■开放科学框架(OSF,项目链接:https://osf.io/r2u4z)。
UNASSIGNED: Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications.
UNASSIGNED: A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture in vitro, in vivo, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies.
UNASSIGNED: Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. In vitro studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of in vitro studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported.
UNASSIGNED: Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together.
UNASSIGNED: Open Science Framework (OSF, project link: https://osf.io/r2u4z).