左布比卡因临床应用研究概述

左布比卡因是新型长效酰胺类局部麻醉药,是布比卡因的左旋异构体。其神经毒性和心脏毒性均低于布比卡因,因而具有更广泛的临床用途。本文主要针对近几年来左布比卡因的临床应用作简要综述。     

布比卡因的心脏毒性作用

布比卡因的心脏毒性作用张毅综述莫治强审校布比卡因（Ｂｕｐｉｖａｃａｉｎｅ）是临床常用局麻药，在临床剂量使用范围内是一个安全、有效的局麻药，但逾量中毒时可致严重的毒性反应，抢救成功率非常低。自七十年代末首次报道因意外将布比卡因大量注入血管而发生心跳骤停...     

左旋布比卡因与布比卡因用于剖宫产术的麻醉效应比较

临床应用广泛的酰胺类长效局麻药布比卡因为消旋化合物,其中枢神经系统和心脏毒性主要来源于R（＋）型镜像体,而S（-）型在体内分布广,清除快,毒性小,将其从消旋化合物中单独提取制成的新型局麻药左旋布比卡因,其药代及药理学特性与布比卡因相仿,而毒性较小,临床安全性明显提高。本研究比较左旋布比卡因和布比卡因用于剖宫术病人硬膜外阻滞效应。     

0.25%和0.375%左旋布比卡因用于臂丛阻滞患者的对比

左旋布比卡因（LBUP）是一种长效的酰胺类局麻药,其结构与布比卡因（BUP）相似,左旋布比卡因是布比卡因是左旋镜像体纯提取物,中枢神经毒性及心脏毒性比布比卡因低,应用与临床及术后镇痛较布比卡因更为优越[1]。本研究观察0.25%和0.375%LBUP及0.375%LBUP含1：20万肾上腺素用于臂丛的临床效果和安全性。1资料与方法1.1一般资料60例行择期手术患者,其中男40例,女20     

左旋布比卡因的临床药理学特点和毒性

长效酰胺类局麻药布比卡因是两种镜像体的消旋混合体,自用于临床后其潜在的心脏毒性引起人们的注意,研究表明其毒性与结构有关,中枢神经系统和心脏毒性主要来源于右旋体.左旋布比卡因是一种临床效果与布比卡因非常类似的长效局麻药,实验室和人体试验资料表明其安全性和毒性优于布比卡因,为临床上更加安全合理地使用左旋布比卡因提供了依据.本文就左旋布比卡因的临床药理学特点和毒性作一综述.     

罗哌卡因用于臂丛麻醉的药效学影响的研究

罗哌卡因是一种新、长效酰胺类局麻药，是甲哌卡因和布比卡因的衍生物，为纯S镜像体。其脂溶性大于利多卡因，但小于布比卡因。与布比卡因一样，罗哌卡因具有很强的血浆蛋白结合力，主要与仅，酸糖蛋白结合。临床前研究表明，罗哌卡因对中枢神经系统和心血管的的毒性比布比卡因小，但比利多卡因大，可能是由于它们在心脏钠离子通道中的蓄积阻滞作用不同，从而导致不同局麻药在心脏毒性方面的差异。     

罗哌卡因/左旋罗哌卡因在麻醉和神经阻滞与术后镇痛中的应用进展

布比卡因是临床应用最为广泛的长效局麻药之一。近年来新型长效局麻药罗哌卡因及左旋布比卡因的临床应用,为临床麻醉、神经阻滞和术后镇痛提供了较为理想的选择。罗哌卡因是一种新型长效酰胺类局麻药。为甲哌卡因、丁卡因的左旋异构体。与布比卡因相比,具有感觉阻滞与运动阻滞分离更趋明显,也有代谢快,对心脏毒性小等特点[1]。左旋布比卡因也是长效酰胺类局麻药,是布比卡因的左旋体。布比卡因是左旋体和右旋体等量混合的消旋体型。     

盐酸左旋布比卡因用于蛛网膜下腔阻滞的研究进展

左旋布比卡因（levobupivacaine）是一种被广泛用于脊椎麻醉的长效酰胺类局麻药布比卡因（bupivacaine）的左旋体，多年来研究表明布比卡因的中枢神经和心脏毒性主要来源于右旋型镜像体，而左旋型在体内分布广，消除慢，机体毒性小，将其从消旋混合物中提取出来而制成的新型局麻药。其麻醉效能与布比卡因相似，但去掉了右旋体，所以神经和心脏毒性明显降低，使用更安全。     

罗哌卡因与布比卡因临床应用研究

岁哌卡因(Rop)是一种新型长效酰胺类局麻药,与布比卡因(Bup)有相似的化学结构和药理特性,心脏毒性低于布比卡因,多用于神经阻滞和硬膜外麻醉[1],本文观察了罗哌卡因与布比卡因在腰麻-硬膜外联合阻滞的临床应用效果.     

等比重左旋布比卡因蛛网膜下腔阻滞在剖宫产的临床应用

<正>左旋布比卡因是一种新型的长效酰胺类局部麻醉药,是布比卡因的左旋镜像体,因其神经毒性和心血管毒性低于布比卡因,而麻醉效能与布比卡因相似,已广泛应用于临床。左旋布比卡因用于蛛网膜下腔阻滞时具有起效迅速、     

Cardiac and CNS toxicity of levobupivacaine: strengths of evidence for advantage over bupivacaine.

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.     

STEREOCHEMISTRY IN ANAESTHESIA

1. Interest in the pharmacokinetic and pharmacodynamic properties of the enantiomers of chiral drugs has greatly increased in recent years. This is particularly so for agents used in anaesthesia. 2. Chiral compounds are those that can exist in two non-superimposable forms. Each form is termed an enantiomer or stereoisomer. Two naming systems are in use: one uses the terms (+) and (–) to indicate the direction the compound will rotate polarized light, while the other system, based on the absolute three-dimensional structure of the enantiomers, uses the terms R and S. 3. Investigation of the stereoisomers of the volatile anaesthetic agent isoflurane is increasing our understanding of the mechanism of general anaesthesia. Current evidence suggests a protein, rather than a lipid, receptor site. 4. Investigation of the stereoisomers of local anaesthetics is increasing the safety of these drugs. 5. For bupivacaine, a widely used amide local anaesthetic, important enantiomeric differences can be found for toxicity, clinical effect and pharmacokinetics. In particular S-(–)-bupivacaine has an improved central nervous system and cardiac safety profile. This is partly explained by the pharmacokinetic differences. 6. Based on these differences, ropivacaine, a propyl homo-logue of bupivacaine, has been produced solely as the S-(–)-enantiomer. The available evidence suggests significantly improved safety for this agent over racemic bupivacaine.     

Direct cardiac effects of intracoronary bupivacaine, levobupivacaine and ropivacaine in the sheep

1. The racemic local anaesthetic agent bupivacaine is widely used clinically for its long duration of action. Levobupivacaine and ropivacaine are bupivacaine enantiopure congeners, developed to improve upon the clinical safety of bupivacaine, especially the risk of fatal arrhythmogenesis. 2. In previous preclinical studies of the safety of these drugs with intravenous administration in conscious ewes over a wide dose range, we found that central nervous system (CNS) excito-toxicity reversed the cardiac depressant effects when doses approached the convulsant threshold and thus precluded accurate comparison of their cardiovascular system (CVS) effects. 3. To study CVS effects over a wide range of doses with minimal CNS and other influences, brief (3 min) infusions of bupivacaine, levobupivacaine or ropivacaine were administered into the left main coronary arteries of previously instrumented conscious ewes (approximately 50 Kg body weight). After dose-ranging studies, the drugs were compared in a randomized, blinded, parallel group design. Equimolar doses were increased from 8 micromol (approximately 2.5 mg) in 8 micromol increments, to either a fatal outcome or a 40 micromol (approximately 12.5 mg) maximum. 4. All three drugs produced tachycardia, decreased myocardial contractility and stroke volume and widening of electrocardiographic QRS complexes. Thirteen of 19 animals died of ventricular fibrillation: four of six with bupivacaine (mean+/-s.e.mean actual fatal dose: 21.8+/-6.4 micromol), five of seven with levobupivacaine (22.9+/-3.5 micromol), four of six with ropivacaine (22.9+/-5.9 micromol). No significant differences in survival or in fatal doses between these drugs were found. 5. The findings suggest that ropivacaine, levobupivacaine and bupivacaine have similar intrinsic ability to cause direct fatal cardiac toxicity when administered by left intracoronary arterial infusion in conscious sheep and do not explain the differences between the drugs found with intravenous dosage.     

Beta-estradiol acutely potentiates the depression of cardiac excitability by lidocaine and bupivacaine.

Pregnancy is known to increase myocardial susceptibility to bupivacaine-induced cardiovascular collapse, and prolonged pretreatment of rabbits with high doses of progesterone potentiates bupivacaine's depression of the maximal rate of increase (Vmax) of the cardiac action potential. Short-term effects of progesterone are not detected in vitro, but other steroids elevated during pregnancy might be acutely active in this model. These experiments tested whether acute exposure to beta-estradiol potentiates local anesthetic/antiarrhythmic depression of Vmax and conduction velocity in rabbit cardiac tissue in vitro. Standard intracellular microelectrodes were used to measure electrophysiologic changes produced by beta-estradiol, local anesthetics, or both in dissected segments of heart containing the Purkinje fiber and ventricular muscle cells from ovariectomized rabbits. In tissues preincubated in beta-estradiol (3.3 nM), addition of bupivacaine (10.4 microM), or lidocaine (85.4 and 129 microM) decreased Vmax significantly more than in steroid-free Tyrode's (p<0.001). Alone, beta-estradiol had no effect on Vmax and depression of Vmax by the nonanesthetic Na+ channel blocker tetrodotoxin (TTX, 3 microM) was not potentiated by beta-estradiol. In preparations initially exposed to bupivacaine for 30 min, subsequent addition of beta-estradiol decreased Vmax further within 10 min (p<0.05). Bupivacaine's greater depression of Vmax at higher frequencies (3 Hz) was exaggerated by beta-estradiol. However, the rate-dependent slowing of conduction by bupivacaine was lessened or even reversed by beta-estradiol addition. Such rapid physiologic changes cannot be due to genomic actions by the hormone that take hours to manifest. Nor is the potentiation due to a general decrease in membrane excitability because the comparable inhibition by TTX is insensitive to estradiol. Because beta-estradiol potentiates the inhibition of myocardial excitability, but alleviates the slowing of impulse conduction between the Purkinje fiber and ventricular muscle produced by local anesthetics, the hormone must produce changes in more than one ionic conductance. Both pregnancy and conditions that abnormally alter levels of steroid hormones have ramifications for local anesthetic-induced cardiotoxicity and antiarrhythmic pharmacotherapeutics.     

EFFECTS OF ALBUMIN ON THE DISPOSITION OF MORPHINE AND MORPHINE-3-GLUCURONIDE IN THE RAT ISOLATED PERFUSED LIVER

1. The effect of albumin on the disposition of morphine and hepatically generated morphine-3-glucuronide (M3G) was investigated in the single-pass rat isolated perfused liver. 1. Interest in the pharmacokinetic and pharmacodynamic properties of the enantiomers of chiral drugs has greatly increased in recent years. This is particularly so for agents used in anaesthesia. 2. Chiral compounds are those that can exist in two non-superimposable forms. Each form is termed an enantiomer or stereoisomer. Two naming systems are in use: one uses the terms (+) and (–) to indicate the direction the compound will rotate polarized light, while the other system, based on the absolute three-dimensional structure of the enantiomers, uses the terms R and S. 3. Investigation of the stereoisomers of the volatile anaesthetic agent isoflurane is increasing our understanding of the mechanism of general anaesthesia. Current evidence suggests a protein, rather than a lipid, receptor site. 4. Investigation of the stereoisomers of local anaesthetics is increasing the safety of these drugs. 5. For bupivacaine, a widely used amide local anaesthetic, important enantiomeric differences can be found for toxicity, clinical effect and pharmacokinetics. In particular S-(–)-bupivacaine has an improved central nervous system and cardiac safety profile. This is partly explained by the pharmacokinetic differences. 6. Based on these differences, ropivacaine, a propyl homo-logue of bupivacaine, has been produced solely as the S-(–)-enantiomer. The available evidence suggests significantly improved safety for this agent over racemic bupivacaine.     

罗哌卡因和布比卡因对心脏毒性作用的比较

目的 :探讨 1%罗哌卡因和 0 .75 %布比卡因用于硬膜外麻醉时对心脏的毒性作用。方法 :选择择期硬膜外麻醉患者 4 0例 ,ASAⅠ级～Ⅱ级。随机分为罗哌卡因组 (R组 ,2 0例 )和布比卡因组 (B组 ,2 0例 ) ,分别于麻醉前 (T0 )和麻醉平面绝对后 (T1)抽取静脉血 3mL ,测定血清心肌肌钙蛋白I(cTnI)的浓度 ,CK MB与CK的活性 ,记录相应时点的MAP ,HR和SpO2 值。结果 :两组患者于麻醉平面绝对后相应指标均较麻醉前有所增高 (P <0 .0 1)。两组间相比麻醉平面绝对后相应指标R组低于B组 ,但无统计学意义 (P >0 .0 5 )。结论 :罗哌卡因用于硬膜外麻醉时对心脏的毒性作用小于布比卡因 ,对血流动力学的影响小 ,用于心脏病非心脏手术的患者较布比卡因安全可靠。     

布比卡因与不同局麻药联用对臂丛麻醉药效的影响

目的比较不同剂量布比卡因单用或与普鲁卡因和利多卡因联合应用对臂丛神经阻滞麻醉作用起效与维持时间的影响。方法选用上肢肘部以下手术8068例 ,按一针法穿刺单次给药作腋路臂丛神经阻滞 ,根据使用药物不同 ,随机分为单独布比卡因或布比卡因混合普卡因和利多卡因三类 ,A、B(含肾上腺素0.2mg)两大组 ,每大组按使用布比卡因剂量不同又分为6小组。结果布比卡因混合利多卡因类较单独布比卡因和布比卡因混合普鲁卡因类作用起效时间短 ,维持时间长(P<0.05或P<0.01) ,加用肾上腺素 ,布比卡因不论何种用药剂量均较同种剂量者长(P<0.01) ;布比卡因大剂量与小剂量比较 ,其作用起效时间与维持时间均呈梯度下降。结论所有组方均可安全用于手外科上肢手术的麻醉 ,尤其适用于不同病因、体质、手术时间病人的选用     

Cardiotoxic local anesthetics increasingly interact with biomimetic membranes under ischemia-like acidic conditions

The cardiotoxic effects of local anesthetics increase in cardiac ischemia which is characterized by the tissue pH lowering to 6.5 or less. Apart from the cardiac channel blockade, the membrane interaction has been referred to as another mode of their cardiotoxic action. By using biomimetic membranes, we verified the hypothesis that bupivacaine and lidocaine may increasingly interact with cardiac mitochondrial membranes under ischemia-like acidic conditions. Biomimetic membranes were prepared with different phospholipids and cholesterol to be unilamellar vesicles suspended in buffers of pH 7.4, 6.9, 6.4 or 5.9. Bupivacaine and lidocaine were reacted with the membrane preparations at cardiotoxically relevant concentrations and their membrane interactivities were determined by measuring fluorescence polarization. Both drugs interacted with 100 mol% 1,2-dipalmitoylphosphatidylcholine, peripheral nerve cell-mimetic and cardiomyocyte-mimetic membranes to increase membrane fluidity, although lowering the reaction pH from 7.4 to 5.9 decreased their membrane-fluidizing effects. In cardiomyocyte mitochondria-mimetic membranes containing 20 mol% cardiolipin, however, bupivacaine and lidocaine reversely increased their membrane interactivities at pH 5.9-6.4 compared with pH 7.4. Such increases were greater in anionic phospholipid membranes which consisted of substantial amounts of cardiolipin and phosphatidylserine. Positively charged bupivacaine and lidocaine would form ion-pairs with the negatively charged head-groups of anionic phospholipids under acidic conditions, thereby increasing the induced membrane fluidization. The mitochondrial membrane interactions depending on pH lowering may be, at least in part, responsible for local anesthetic cardiotoxicity enhanced in acidosis associated with cardiac ischemia.     

The protective effect of lipid emulsion in preventing bupivacaine-induced mitochondrial injury and apoptosis of H9C2 cardiomyocytes

Lipid emulsion (LE) has been shown to be effective in the resuscitation of bupivacaine-induced cardiac arrest, but the precise mechanism of this action has not been fully elucidated. Pursuant to this lack of information on the mechanism in which LE protects the myocardium during bupivacaine-induced toxicity, we explored mitochondrial function and cell apoptosis. H9C2 cardiomyocytes were used in study. Cells were randomly divided in different groups and were cultivated 6?h, 12?h, and 24?h. The mitochondria were extracted and mitochondrial ATP content was measured, as was mitochondrial membrane potential, the concentration of calcium ion (Ca2+), and the activity of Ca2+-ATP enzyme (Ca2+-ATPase). Cells from groups Bup1000, LE group, and Bup1000LE were collected to determine cell viability, cell apoptosis, and electron microscopy scanning of mitochondrial ultrastructure (after 24?h). We found that LE can reverse the inhibition of the mitochondrial function induced by bupivacaine, regulate the concentration of calcium ion in mitochondria, resulting in the protection of myocardial cells from toxicity induced by bupivacaine.