Gristwood R W, Greaves J L
Arachnova Ltd., St John's Innovation Centre, Cambridge, CB4 OWS, UK.
Expert Opin Investig Drugs. 1999 Jun;8(6):861-76. doi: 10.1517/13543784.8.6.861.
The choice of local anaesthetic is influenced by several factors; it must provide effective anaesthesia and analgesia for the duration of the procedure and meet the expectations for post-operative pain management. Of primary concern is patient safety. Bupivacaine, currently the most widely used long acting local anaesthetic agent in both surgery and obstetrics, generally has a good safety record but its use has resulted in fatal cardiotoxicity, usually after accidental intravascular injection. Hence, for several years there has been a need for a long acting local anaesthetic, similar to bupivacaine, but with an improved cardiovascular safety profile. Levobupivacaine, the single enantiomer version of bupivacaine, offers a new long acting local anaesthetic, clinically equivalent in anaesthetic potency to bupivacaine, but with a reduced toxicity profile. Preclinical studies, from in vitro in single ion channels to whole large animal models, have unquestionably demonstrated that levobupivacaine is significantly less CNS toxic and cardiotoxic than bupivacaine. Cardiotoxicity is less easy to study in man, as the clinical signs are not usually seen until the CNS toxicity is marked, and well beyond that which is tolerable to volunteers or patients. Nevertheless, levobupivacaine has been shown to have less effect on myocardial contractility and QTc prolongation, early signs of cardiotoxicity, than bupivacaine in healthy subjects. In clinical use levobupivacaine has been shown to be equally efficacious as bupivacaine at comparable doses and concentrations, and has been found to produce similar anaesthetic characteristics (onset, duration and density of block). As levobupivacaine now becomes commercially available, the database available with which to make efficacy and safety comparisons with other local anaesthetics will increase, and the true value of this new long acting local anaesthetic should become even more apparent.
局部麻醉药的选择受多种因素影响；它必须在手术过程中提供有效的麻醉和镇痛，并满足术后疼痛管理的期望。首要关注的是患者安全。布比卡因是目前外科手术和产科中使用最广泛的长效局部麻醉药，总体上有良好的安全记录，但它的使用已导致致命的心脏毒性，通常发生在意外血管内注射之后。因此，多年来一直需要一种类似于布比卡因的长效局部麻醉药，但具有更好的心血管安全性。左旋布比卡因是布比卡因的单一异构体形式，提供了一种新的长效局部麻醉药，其麻醉效力在临床上与布比卡因相当，但毒性更低。从单离子通道的体外研究到整个大型动物模型的临床前研究，无疑已经证明左旋布比卡因的中枢神经系统毒性和心脏毒性明显低于布比卡因。心脏毒性在人体中较难研究，因为临床体征通常直到中枢神经系统毒性明显时才会出现，而且远远超出志愿者或患者可耐受的程度。然而，在健康受试者中，已证明左旋布比卡因对心肌收缩力和QTc延长（心脏毒性的早期迹象）的影响小于布比卡因。在临床使用中，已证明左旋布比卡因在可比剂量和浓度下与布比卡因同样有效，并且已发现其产生相似的麻醉特性（阻滞的起效、持续时间和密度）。随着左旋布比卡因现在开始商业化，可用于与其他局部麻醉药进行疗效和安全性比较的数据库将会增加, 这种新型长效局部麻醉药的真正价值应该会变得更加明显。
