Schäfer M, Mousa S A, Shaqura M, Tafelski S
Klinik für Anästhesiologie mit S. op. Intensivmedizin, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland.
Anaesthesist. 2019 Jan;68(1):3-14. doi: 10.1007/s00101-018-0522-6.
The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.
通过阻断钠离子通道发现局部麻醉作用是麻醉领域的一个里程碑,但很快就受到局部麻醉药有时会危及生命的毒性作用的限制。通过开发新型局部麻醉药以及添加所谓的佐剂,人们试图限制这些危及生命的事件。本文重点关注这些佐剂用于区域麻醉的历史背景和当前使用状况。添加肾上腺素、可乐定或右美托咪定,但仅单次给药,会使区域麻醉的起效更快、作用持续时间更长且神经阻滞强度增加。另一方面,添加碳酸氢钠的益处相对较小,因此在临床上可忽略不计。尽管文献中越来越多的证据表明轴突给药阿片类药物后镇痛效果有所改善和延长,且阿片类药物也可连续给药,但由于中枢副作用发生率增加,全身作用仍不能完全排除。阿片类药物的部分局部麻醉作用并不总是能与阿片受体特异性作用区分开来。机制研究推测阿片受体在受损而非完整的外周神经中发生功能偶联。最近的研究已确定糖皮质激素和盐皮质激素受体主要存在于外周伤害性神经纤维上。这与众多关于局部麻醉作用显著延长的临床报告一致。除了类固醇通过改变维持疼痛的蛋白质结构的基因表达而产生的已知基因组效应外,还讨论了通过细胞内信号通路改变而产生的更快的非基因组效应。总之,对机制的新见解和临床试验的新结果将有助于麻醉医生决定是否使用佐剂进行区域麻醉,然而,这需要权衡个体患者的获益与风险。