Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

中文翻译：

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局部麻醉剂混合物的药理学和临床意义：叙述性综述

已经探索了各种技术来延长局部麻醉神经阻滞的持续时间并提高其功效。其中一些涉及混合局部麻醉剂或添加辅助剂。我们对 2011 年 5 月 1 日至 2021 年 5 月 1 日期间发表的研究进行了文献综述，这些研究研究了局部麻醉剂和辅助剂的特定组合。混合长效和短效局部麻醉剂以加速起效和延长持续时间的基本原理在药代动力学原理上存在缺陷。大多数局部麻醉剂未获准以这种方式使用，未经测试的外加剂和辅助剂的后果从使解决方案无效到潜在危害不等。给药前需要建立药物相容性。无法推断同一类药物的相容性，每种混合物都需要单独审查。混合沉淀（类固醇、非甾体抗炎药）和随后的栓塞可导致严重的不良事件，尽管这些情况很少见。添加剂本身或其防腐剂可能具有神经毒性（肾上腺素、咪达唑仑）和/或软骨毒性（非甾体抗炎药）。阻滞的延长可能会以运动阻滞质量（氯胺酮）或阻滞开始（镁）为代价。一些辅助剂的副作用似乎与剂量有关，并且缺乏关于最佳剂量的建议。一个重要的混杂因素是研究是否使用系统性辅助给药作为对照，以准确确定神经周围给药的额外益处。