Timour Q, Gaillard P, Bui-Xuan B, Vial T, Evreux J C, Freysz M
Pharmacologie Médicale, Université Claude Bernard, Lyon.
Bull Acad Natl Med. 1998;182(2):217-32.
Cardiac disorders are observed when excessive plasma concentrations of local anaesthetics are reached, following for instance intravascular accidental injection for epidural anaesthesia or brachial plexus block. Bupivacaine particularly, which is one of the most used local anaesthetics, adversely affects intraventricular conduction and cardiac contractile strength from the 3.0-4.0 micrograms/ml blood levels. Depression of conduction is especially to be feared, for it can result in reentrant arrhythmias likely to degenerate into often fatal ventricular fibrillation. Such accidents may sometimes occur at far lower concentrations, subsequent to diffusion into systemic circulation from the injection site (0.4-1.2 micrograms/ml). These accidents were probably due to various factors which concomitantly intervene during the anaesthesia. We could identify a number of these factors by associating them to an intravenous infusion of bupivacaine (0.04 mg/kg/min after a loading dose of 1.00 mg/kg) in animals (dogs and pigs) under electrocardiographic monitoring, in which conduction time, monophasic action potential duration, effective refractory period and electrical fibrillation threshold were determined in the ventricular fibres. The electrophysiological changes due to bupivacaine may be enhanced by 1) dilution hyponatremia (115-110 mmol/l) induced by a short (5 min) intravenous 10 ml/kg/min infusion of hypotonic solution and/or hyperkalemia (7-8 mmol/l) induced by 0.05 mmol/kg/min infusion of potassium chloride; 2) the acceleration of cardiac contractions (180-210 beats/min) induced by ventricular pacing; 3) mild hypothermia (35-34 degrees C) induced by blood cooling in an extracorporeal circuit; 4) myocardial ischaemia induced by complete temporary occlusion of the left anterior descending coronary artery near its origin. The risk of cardiac accidents, possibly severe, is therefore enhanced by each of these factors capable of lowering the concentration required for their triggering and, of course, the combination of two or several of them. On the contrary, the knowledge of these factors should allow to prevent most of cardiac accidents of locoregional anaesthesia.
当局部麻醉药血浆浓度过高时，会出现心脏紊乱，比如在硬膜外麻醉或臂丛神经阻滞时意外血管内注射。尤其是布比卡因，它是最常用的局部麻醉药之一，当血液浓度达到3.0 - 4.0微克/毫升时，会对室内传导和心脏收缩力产生不利影响。传导抑制尤其令人担忧，因为它可能导致折返性心律失常，进而可能恶化为常常致命的心室颤动。此类意外有时可能在远低于该浓度时发生，即在药物从注射部位扩散到体循环后（0.4 - 1.2微克/毫升）。这些意外可能是由于麻醉过程中同时起作用的多种因素所致。我们通过在动物（狗和猪）身上进行心电图监测，将布比卡因静脉输注（负荷剂量1.00毫克/千克后，以0.04毫克/千克/分钟的速度输注）与这些因素相关联，从而确定了其中一些因素。在这个过程中，测定了心室纤维的传导时间、单相动作电位持续时间、有效不应期和电颤动阈值。布比卡因引起的电生理变化可能会因以下因素而增强：1）短时间（5分钟）以10毫升/千克/分钟的速度静脉输注低渗溶液诱导的稀释性低钠血症（115 - 110毫摩尔/升）和/或0.05毫摩尔/千克/分钟的速度输注氯化钾诱导的高钾血症（7 - 8毫摩尔/升）；2）心室起搏诱导的心脏收缩加速（180 - 210次/分钟）；3）体外循环中血液冷却诱导的轻度低温（35 - 34摄氏度）；4）左前降支冠状动脉起始处完全暂时闭塞诱导的心肌缺血。因此，这些能够降低引发心脏意外所需浓度的因素中的每一个，当然还有其中两个或几个因素的组合，都会增加可能严重的心脏意外风险。相反，了解这些因素应该有助于预防大多数局部区域麻醉引起的心脏意外。
