Veering Bernadette T
Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Curr Opin Anaesthesiol. 2003 Oct;16(5):455-9. doi: 10.1097/00001503-200310000-00004.
Local anaesthetic agents are administered every day in clinical practice. These agents are relatively safe when administered in proper dosages at appropiate anatomical sites. However, when excessive dosages are administered or the incorrect site of administration is used there is a potential for toxic reactions. Ropivacaine, a pure S-enantiomer, and levobupivacaine, a single isomer of bupivacaine, have been introduced as new long-acting local anaesthetic agents with a potentially reduced toxicity compared with bupivacaine. The present review deals with recent knowledge about systemically induced local anaesthetic toxicity and localized toxicity.
Studies have compared cardiotoxicity directly between ropivacaine and levobupivacaine in intracoronary injection in sheep and pigs, in small mammals, and arrhythmias and resuscitation in dogs. Direct left coronary arterial infusions of local anaesthetics in a conscious sheep model precludes central nervous system actions. Intracoronary studies showed similar toxicity for levobupivacaine and ropivacaine. When comparing and interpreting in-vivo animal studies of local anaesthetic toxicity, species variations, differences in the mode and site of local anaesthetic administration, and whether the animal is under the influence of anaesthesia must all be considered. Stereoselectivity may play a role in the lengthening of the atrioventricular conduction time for bupivacaine. In-vitro studies have revealed that intracellular calcium concentrations may contribute to myotoxicity.
Current evidence suggests that ropivacaine is slightly less toxic than levobupivacaine; however, the difference in potency between the two agents is greater. The new local anaesthetic agents can be regarded as 'safer', but must not be regarded as safe.
局部麻醉药在临床实践中每日都有应用。这些药物在适当的解剖部位以适当剂量给药时相对安全。然而,当给药剂量过大或给药部位不正确时,就有可能发生毒性反应。罗哌卡因是一种纯S-对映体,左旋布比卡因是布比卡因的单一异构体,已作为新型长效局部麻醉药被引入,与布比卡因相比,其潜在毒性可能降低。本综述探讨了有关全身诱导的局部麻醉药毒性和局部毒性的最新知识。
研究已在绵羊和猪的冠状动脉内注射、小型哺乳动物以及犬的心律失常和复苏方面,对罗哌卡因和左旋布比卡因的心脏毒性进行了直接比较。在清醒绵羊模型中直接向左冠状动脉内输注局部麻醉药可排除中枢神经系统作用。冠状动脉内研究显示左旋布比卡因和罗哌卡因的毒性相似。在比较和解释局部麻醉药毒性的体内动物研究时,必须考虑物种差异、局部麻醉药给药方式和部位的差异以及动物是否处于麻醉影响之下。立体选择性可能在布比卡因延长房室传导时间方面起作用。体外研究表明细胞内钙浓度可能与肌毒性有关。
目前的证据表明罗哌卡因的毒性略低于左旋布比卡因;然而,这两种药物之间的效能差异更大。新型局部麻醉药可被视为“更安全”,但绝不能被视为安全。