Gristwood Robert W
Arachnova Limited, St John's Innovation Centre, Cambridge, United Kingdom.
Drug Saf. 2002;25(3):153-63. doi: 10.2165/00002018-200225030-00002.
Bupivacaine is currently the most widely used long-acting local anaesthetic. Its uses include surgery and obstetrics; however, it has been associated with potentially fatal cardiotoxicity, particularly when given intravascularly by accident. Levobupivacaine, a single enantiomer of bupivacaine, has recently been introduced as a new long-acting local anaesthetic with a potentially reduced toxicity compared with bupivacaine. Numerous preclinical and clinical studies have compared levobupivacaine with bupivacaine and in most but not all studies there is evidence that levobupivacaine is less toxic. Advantages for levobupivacaine are seen on cardiac sodium and potassium channels, on isolated animal hearts and in whole animals, anaesthetised or awake. In particular the intravascular dose of levobupivacaine required to cause lethality in animals is consistently higher compared with bupivacaine. In awake sheep, for example, almost 78% more levobupivacaine was required to cause death. In contrast, in anaesthetised dogs no differences were seen in the incidence of spontaneous or electrical stimulation- induced ventricular tachycardia and fibrillations among animals exposed to levobupivacaine or bupivacaine. The reversibility of levobupivacaine-induced cardiotoxicity has also been assessed. Some data point to an advantage of levobupivacaine over bupivacaine but this potential advantage was not confirmed in a recent study in anaesthetised dogs. Three clinical studies have been conducted using surrogate markers of both cardiac and CNS toxicity. In these studies levobupivacaine or bupivacaine were given by intravascular injection to healthy volunteers. Levobupivacaine was found to cause smaller changes in indices of cardiac contractility and the QTc interval of the electrocardiogram and also to have less depressant effect on the electroencephalogram. Assuming that levobupivacaine has the same local anaesthetic potency as bupivacaine, then, all things being equal, it is difficult to argue that levobupivacaine should not displace bupivacaine as the long-acting local anaesthetic of choice. It would appear, however, that levobupivacaine has not yet significantly displaced bupivacaine from the markets in which it is sold. This may be due to a lack of perceived safety benefit and/or consideration of the additional costs that are associated with switching to levobupivacaine, which is approximately 57% more expensive than bupivacaine. If the price of levobupivacaine were closer to bupivacaine then the argument to switch to levobupivacaine would undoubtedly be much stronger. With the continued clinical use of levobupivacaine the database available to make comparisons will increase and this may allow cost-benefit arguments to be made more forcefully for levobupivacaine in the future.
布比卡因是目前使用最广泛的长效局部麻醉剂。其用途包括外科手术和产科；然而，它与潜在的致命性心脏毒性有关，尤其是意外血管内给药时。左旋布比卡因是布比卡因的单一对映体，最近作为一种新的长效局部麻醉剂被引入，与布比卡因相比，其潜在毒性可能降低。大量临床前和临床研究对左旋布比卡因和布比卡因进行了比较，在大多数但并非所有研究中，有证据表明左旋布比卡因毒性较小。在心脏钠通道和钾通道、离体动物心脏以及麻醉或清醒的整体动物中，均可观察到左旋布比卡因的优势。特别是，与布比卡因相比，导致动物死亡所需的左旋布比卡因血管内剂量一直更高。例如，在清醒绵羊中，导致死亡所需的左旋布比卡因几乎多78%。相比之下，在麻醉犬中，暴露于左旋布比卡因或布比卡因的动物中，自发性或电刺激诱发的室性心动过速和颤动的发生率没有差异。也评估了左旋布比卡因诱导的心脏毒性的可逆性。一些数据表明左旋布比卡因优于布比卡因，但最近一项对麻醉犬的研究未证实这一潜在优势。已经进行了三项使用心脏和中枢神经系统毒性替代标志物的临床研究。在这些研究中，将左旋布比卡因或布比卡因血管内注射给健康志愿者。发现左旋布比卡因引起的心脏收缩力指标和心电图QTc间期变化较小，对脑电图的抑制作用也较小。假设左旋布比卡因与布比卡因具有相同的局部麻醉效能，那么在其他条件相同的情况下，很难说左旋布比卡因不应取代布比卡因成为首选的长效局部麻醉剂。然而，似乎左旋布比卡因尚未在其销售市场上显著取代布比卡因。这可能是由于缺乏明显的安全益处和/或考虑到改用左旋布比卡因相关的额外成本，左旋布比卡因比布比卡因贵约57%。如果左旋布比卡因的价格更接近布比卡因，那么改用左旋布比卡因的理由无疑会更充分。随着左旋布比卡因的持续临床使用，可用于比较的数据库将增加，这可能会使未来支持左旋布比卡因的成本效益论据更有说服力。
