Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats

BACKGROUND AND OBJECTIVE: Clonidine has cardiac and systemic effects that can modify the potentially lethal cardiovascular effects of local anaesthetics. We evaluated the effects of clonidine pre-treatment on cardiotoxicity induced by an infusion of bupivacaine or ropivacaine and the success rate of resuscitation in anaesthetized rats. METHODS: Thirty-two Sprague-Dawley rats (250-300 g) were anaesthetized with thiopental and ketamine. Lung ventilation was maintained mechanically, and the electrocardiograph and invasive blood pressure were recorded continuously. Two separate groups of rats were treated with intravenous clonidine 5 microg kg(-1) (n = 16) or saline (n = 16) in a randomized fashion. Fifteen minutes later, each group was randomly subdivided into two equal groups and an infusion of bupivacaine or ropivacaine, 3 mg kg(-1) min(-1), was given until cardiac arrest (asystole) occurred. The times when the cardiotoxic events (25%, 50% and 75% reduction of arterial pressure and heart rate, first dysrhythmia and asystole, respectively), induced by the local anaesthetic, occurred and the resuscitation outcome scores were recorded. RESULTS: Clonidine reduced heart rate and arterial pressure (P < 0.01). Clonidine did not alter cardiotoxicity or the success rate of resuscitation in bupivacaine-treated rats. In the ropivacaine group, clonidine increased the 25%, 50% and 75% reduction times of arterial pressure and the 50% and 75% reduction times of heart rate, times to first dysrhythmia and asystole (P < 0.05). Clonidine also increased the success rate of resuscitation in ropivacaine-treated rats (P < 0.05). CONCLUSIONS: Although pre-treatment with clonidine protects the effects of ropivacaine cardiotoxicity and increases the success rate of resuscitation, it does not affect bupivacaine toxicity.     

Hyperbaric ropivacaine and bupivacaine

Editor—Whiteside and colleagues¹ in their comparison ofhyperbaric ropivacaine and bupivacaine for spinal anaesthesiastate that ‘the key issue is the difference in clinicalprofile of the block...not the relative potencies of the twodrugs’. It would have been much easier     

Differences in cardiac toxicity among ropivacaine,levobupivacaine, bupivacaine,and lidocaine

Local-anesthetic (LA) cardiotoxicity remains a vexing issue in clinical practice. Growing demand for integration of regional and general anesthesia with acute pain management mandates that the contemporary anesthesiologist be knowledgeable about LA capabilities and toxicity. Although various LA agents are available for clinical use, they often must meet the requirements for both acute, intraoperative regional anesthesia and subacute, postoperative regional anesthesia. Usually, the long-acting LAs (historically, bupivacaine) fulfill these needs. However, when large volumes of concentrated LA are needed to shorten latency and increase duration, systemic toxicity may become an issue. For this reason, the newer, long-acting, amide LAs, ropivacaine and levobupivacaine, were developed; both are touted to have less cardiotoxic potential than bupivacaine. This report reviews normal impulse conduction and cardiac contraction, as well as the basic physiology and pharmacology of LA-induced cardiotoxicity. In addition, safety concerns with the long-acting LAs, current laboratory data on cardiac toxicity from these agents, and the implications of the data for clinical practice are reviewed. Copyright © 2001 by W.B. Saunders Company     

Extradural ropivacaine and bupivacaine in hip surgery

We studied 126 patients undergoing elective hip surgery; theyreceived 20 ml of 0.5%, 0.75%, 1.0% ropivacaine or 0.5% bupivacaineextradurally in a double-blind design. Sensory block (pinprick),motor block (modified Bromage scale), quality of analgesia andneuromuscular block were assessed intermittently. Heart rateand arterial pressure were measured at regular intervals. Atotal of 115 patients were evaluated for efficacy. Onset ofanalgesia, onset of motor block and maximum cephalad spread(T4) did not differ between the groups. Duration and qualityof analgesia and motor block increased with the concentrationof ropivacaine. Ropivacaine 1.0% provided a longer durationof analgesia and motor block, more intense motor block and morepatients with satisfactory analgesia than 0.5% bupivacaine.More patients treated with the higher concentrations of ropivacainerequired treatment for hypotension and bradycardia.     

Sufentanil modifies the antibacterial activity of bupivacaine and ropivacaine

PURPOSE: The purpose of our study was to investigate the effect on the growth of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Enterococcus faecalis (E. faecalis) of bupivacaine at a final concentration of 0.77 mg.mL(-1), ropivacaine at 1.2 mg.mL(-1), and sufentanil at 0.38 and 0.5 microg.mL(-1) (alone or in combination with bupivacaine and ropivacaine). METHODS: The strains were diluted to approximately 3 x 10(4) cfu.mL(-1) in Mueller-Hinton broth. The anesthetics (0.5 mL) were incubated with the bacterial suspensions (0.5 mL) for 24 hr at 37 degrees C. RESULTS: Bupivacaine inhibited the growth of E. coli (59 +/- 0.8%; P < 0.05) and S. aureus (22 +/- 3.6%; P < 0.05). Ropivacaine also inhibited the growth of E. coli (41 +/- 1.2%; P < 0.05) and S. aureus (25.5 +/- 4.1%; P < 0.05). Both anesthetics were ineffective against E. faecalis. Sufentanil only inhibited S. aureus (13.8 +/- 3.1%; P < 0.05) at a concentration of 0.5 microg.mL(-1). Sufentanil modified the antibacterial activity of bupivacaine and ropivacaine. It increased the inhibitory effect of bupivacaine on E. faecalis and S. aureus by 10 +/- 2.1% (P < 0.05) and on E. coli by 7% (P < 0.05). Sufentanil did not increase the inhibitory effect of ropivacaine on the growth of S. aureus. On the other hand, sufentanil reduced the inhibitory effect of ropivacaine on E. coli by 11% (P < 0.05). CONCLUSION: Both bupivacaine and ropivacaine alone or combined with sufentanil inhibited the growth of E. coli and S. aureus. E. faecalis was partially sensitive to a bupivacaine + sufentanil mixture. Sufentanil had a partial synergistic effect on bupivacaine and a partial antagonistic effect on ropivacaine's antibacterial activity.     

Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart

This study was designed to compare the direct actions of bupivacaine and lidocaine on the isolated perfused guinea pig Langendorff heart preparation. Sixty min after mounting, either bupivacaine HCl (0.3 or 3 micrograms/ml) or lidocaine HCl (10 or 30 micrograms/ml) was added to the perfusate, and the effect (if any) was compared to untreated control values 30, 60, and 90 min later. Although the highest concentrations of both drugs invariably produced statistically significant reductions in heart rate, df/dt, coronary blood flow, and myocardial oxygen consumption (MVO2), these reductions were consistently greater after bupivacaine. Moreover, arrhythmias occurred in 6 of 12 preparations in those hearts exposed to 3 micrograms/ml of bupivacaine. Most often these arrhythmias consisted of heart block and bi- or trigeminy. Additional studies indicated that the reduction in coronary blood flow and MVO2 produced by 3 micrograms/ml of bupivacaine was a consequence of its direct negative inotropic and chronotropic action. Although the myocardial depression produced by bupivacaine and lidocaine could be reversed readily by substituting fresh perfusate, increasing the extracellular calcium concentration in stepwise increments did not augment the negative inotropic or chronotropic effect produced by 3 micrograms/ml of bupivacaine or 10 micrograms/ml of lidocaine. We conclude that 3 micrograms/ml of unbound bupivacaine is more cardiotoxic than 30 micrograms/ml of unbound lidocaine in this model.     

Relative potencies of bupivacaine and ropivacaine for analgesia in labour

We have used the technique of randomized, double-blind sequential allocation to compare the minimum local analgesic concentrations (MLAC) of epidural bupivacaine and ropivacaine for women in the first stage of labour. The test bolus was 20 ml of local anaesthetic solution. The concentration was determined by the response of the previous woman to a higher or lower concentration of local anaesthetic, according to up- down sequential allocation. Efficacy was assessed using a 100-mm visual analogue pain score (VAPS). The test solution had to achieve a VAPS of 10 mm or less to be judged effective. For bupivacaine, MLAC was 0.093 (95% CI 0.076-0.110)% w/v, and for ropivacaine, 0.156 (95% CI 0.136- 0.176)%w/v (P < 0.0001, 95% CI difference 0.036-0.090). The analgesic potency of ropivacaine was 0.60 (0.47-0.75) relative to bupivacaine. Claims for reduced toxicity and motor block must be considered with differences in analgesic potency in mind.      

Comparative efficacy of ropivacaine and bupivacaine infiltrative analgesia in otoplasty

A prospective double-blind study was conducted to compare the anesthetic efficacy of ropivacaine and bupivacaine in a bilaterally symmetrical otoplasty model. Because ropivacaine has a significantly lower toxic potential than bupivacaine, it may be established as the anesthetic agent of choice for low-dose infiltration anesthesia in routine aesthetic facial operations. Each of the 24 adult patients undergoing bilateral otoplasty received infiltration with ropivacaine in 1 auricle and an equal volume of bupivacaine in the other. Patients were requested to assess their pain separately in each side at the times of infiltration, during cartilage scoring, and 2, 6, and 10 hours postoperatively on a visual analog scale. Intraoperative success rates were similar, and overall analgesia achieved at 2 hours, 6 hours, and 10 hours postoperatively was not found to be statistically different between ropivacaine and bupivacaine. The authors conclude that ropivacaine can be used as an effective alternative to bupivacaine in otoplasty.     

罗比卡因和布比卡因在老年人脊麻中的应用

目的比较罗比卡因和布比卡因在老年人脊麻中的应用。方法90例老年患者在脊麻下行择期经尿道前列腺电切术(TURP)或膀胱肿瘤电切术(TURBt)。按所用局麻药随机分为三组,每组30例。Ⅰ组用布比卡因12mg,Ⅱ组用罗比卡因12mg,Ⅲ组用罗比卡因15mg。观察感觉阻滞平面、运动阻滞程度、阻滞持续时间、麻醉效果及不良反应。结果Ⅱ组运动阻滞程度和感觉、运动阻滞持续时间明显低于其他两组(P<0.05),麻醉效果差于其他两组(P<0.05)。结论罗比卡因15mg与布比卡因12mg脊麻用于老年人TURP或TURBt,可达到比较安全而完善的麻醉效果。     

Effects of bupivacaine and ropivacaine on the isolated human umbilical artery

In this in vitro study on the human umbilical artery, the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME), indomethacin, prazosin, yohimbine and propranolol on the responses induced by bupivacaine and ropivacaine were investigated. Arteries isolated from umbilical cords from women who did not exhibit systemic diseases, who were not on medication and who had normal full-term deliveries, were cut into spiral strips 12 x 3 mm. Strips were mounted in organ baths at 37 degrees C continuously gassed with 5% CO(2) in oxygen. The responses to the drugs were recorded isometrically on a polygraph. In the bupivacaine study, when we administered cumulative concentrations of bupivacaine (10(-9) - 10(-4) M; n = 6) on basal tonus, there was no relaxation or contraction response on the tissue. Strips were precontracted with serotonin (10(-6)M 5-HT) then bupivacaine (10(-9) - 10(-4) M) was directly administered cumulatively. In the ropivacaine group, when cumulative concentrations of ropivacaine (10(-9) - 10(-4) M; n = 6) were administered on the tissue, preconstricted with 5-HT, ropivacaine did not alter the contraction response. Ropivacaine (10(-9) - 10(-4) M) was directly administered to the bath. Though bupivacaine produced relaxation, ropivacaine produced contraction (P < 0.05). Indomethacin, prazosin, yohimbine and propranolol did not significantly alter these responses. In addition, it was demonstrated that L-NAME did not affect the relaxation responses induced by bupivacaine. Thus adrenergic receptors, nitric oxide syntenaze and prostaglandins do not appear to affect the responses induced by these two local anesthetics.     

氨吡酮对离体大鼠灌注心脏布比卡因毒性作用的影响

目的　在离体大鼠灌注心脏模型中观察氨吡酮对布比卡因 (BU P)心脏毒性作用的影响。方法　选用 SD大鼠离体心脏 L angendorff灌注模型 ,随机将大鼠心脏分为三组 ,分别为对照组(组 )、输注 Bup 80μg/ min 15 min(组 )、输注 Bup 80μg/ m in 15 min后 ,输注氨吡酮 80μg/ m in 15 min(组 ) ,观察心率 (HR)、左室舒张末期压 (L VEDP)、左室发展压 (L VDP)、 dp/ dt、- dp/ dt的变化以及心肌 c AMP含量。结果　组 、组 在输注 Bup后 HR,L VDP、 dp/ dt、- dp/ dt值与基础值比较均明显降低 ,而 L VEDP则明显高于基础值 ,而组 在输注氨吡酮后上述指标均得以恢复 ,组 心肌c AMP含量也明显低于组 和组 。结论　氨吡酮逆转 Bup心脏毒性作用可能与其增加心肌组织c AMP含量和改善心肌收缩舒张功能有关。     

罗哌卡因与布比卡因用于硬膜外阻滞麻醉效果的Meta分析

目的 评价罗哌卡因在硬膜外阻滞麻醉应用中的效果与安全性. 方法 检索PubMed、中国学术期刊全文等数据库中罗哌卡因与布比卡因在硬膜外阻滞麻醉的对比研究,利用Meta分析专用软件RevMan 5.0进行系统评价,重点分析罗哌卡因与布比卡因在感觉阻滞起效时间、运动阻滞恢复时间以及低血压发生率间的差异. 结果 12项研究纳入Meta分析,其中罗哌卡因组362例,布比卡因组377例.罗哌卡因与布比卡因比较,具有较短的感觉阻滞起效时间(Z=2.24,P=0.02,I2=20.5％,P＞0.05),与运动阻滞恢复时间(Z=5.70,P＜0.01,I2=58.9％,P＞0.05),但两者低血压发生率差别无统计学意义(Z=1.06,P＞0.05,I22=0,P＞0.05).结论 罗哌卡因麻醉效果确切,运动阻滞恢复快,具有较高的硬膜外阻滞麻醉优越性.     

A comparison of ropivacaine and bupivacaine for cervical plexus block

We compared bupivacaine 0.5% and ropivacaine 0.75% for cervical plexus block (CB). Forty patients scheduled for carotid artery surgery were allocated randomly to undergo superficial and deep CB with 30 mL of one of the two anesthetic solutions. We evaluated the onset of anesthetic block; the requirement for supplementation during the surgery; the patients' satisfaction; postoperative pain on a visual analog scale at 1, 2, and 3 h; and the use of paracetamol as a rescue analgesic medication. Arterial blood was sampled immediately and 1, 3, 5, 10, 15, 30, 45, and 60 min after CB for measurements of bupivacaine or ropivacaine concentrations. Patients in both groups had equivalent onset of CB, local infiltration with lidocaine during surgery, and satisfaction scores. In the Bupivacaine group, visual analog scale scores were lower at 2 and 3 h, and the delay before paracetamol administration was prolonged. Observed peak concentrations were larger in the Ropivacaine group (4.25 [2.07-6.59 mg/L] vs 3.02 [0.98-5.82 mg/L]), but time to reach peak concentrations was comparable (5 [1-15 min] vs 5 [0-45 min] in the Ropivacaine and Bupivacaine groups, respectively). We conclude that ropivacaine has no advantage over bupivacaine for CB. IMPLICATIONS: Compared with bupivacaine (150 mg), a larger dose of ropivacaine (225 mg) produces comparable features of cervical plexus block but less postoperative analgesia and larger plasma concentrations. There is no reason to favor ropivacaine in such a case.     

鞘内注射罗哌卡因与布比卡因对大鼠的脊髓神经毒性

目的 评价鞘内注射罗哌卡因与布比卡因对大鼠的脊髓神经毒性.方法 清洁级雌性SD大鼠,体重240～330 g,取鞘内置管成功的大鼠54只,随机分为3组(n=18):NS组鞘内注射生理盐水30μl;Bu组和RO组分别鞘内注射2%布比卡因20μl和2.7%罗哌卡因20μl,随后注射10μl生理盐水冲洗导管.于鞘内注药前、注药后10、20、30、60和120 min时(T1～6)行双后肢运动阻滞评分;于鞘内注药后第4天取腰段脊髓组织,观察病理学结果并行损伤评分.结果 与NS组比较,BU组T2～5时、RO组T2～4时大鼠双后肢运动阻滞评分升高,两组脊髓组织损伤评分升高(P＜0.05),脊髓组织病理学损伤较重;与T2时比较,Bu组和RO组其余各时点双后肢运动阻滞评分降低(P＜0.05),两组T2时差异无统计学意义(P＞0.05);与BU组比较,RO组脊髓组织损伤评分升高(P＜0.05),脊髓组织病理学损伤较重.结论 鞘内注射2.7%罗哌卡因对大鼠的脊髓神经毒性强于2%布比卡因.     

Acute toxicity of ropivacaine compared with that of bupivacaine

The acute central nervous and cardiovascular effects of the local anesthetics ropivacaine and bupivacaine were compared in 12 volunteers in a randomized double-blind manner with use of intravenous infusions at a rate of 10 mg/min up to a maximal dose of 150 mg. The volunteers were all healthy men. They were familiarized with the central nervous system (CNS) toxic effects of local anesthetics by receiving a preliminary intravenous injection of lidocaine. The infusions of ropivacaine and bupivacaine were given not less than 7 days apart. CNS toxicity was identified by the CNS symptoms and the volunteers were told to request that the infusion be stopped when they felt definite but not severe symptoms of toxicity such as numbness of the mouth, lightheadedness, and tinnitus. In the absence of definite symptoms, the infusion was stopped after 150 mg had been given. Cardiovascular system (CVS) changes in conductivity and myocardial contractility were monitored using an interpretive electrocardiograph (which measured PR interval, QRS duration, and QT interval corrected for heart rate) and echocardiography (which measured left ventricular dimensions from which stroke volume and ejection fraction were calculated). Ropivacaine caused less CNS symptoms and was at least 25% less toxic than bupivacaine in regard to the dose tolerated. Both drugs increased heart rate and arterial pressure. Stroke volume and ejection fraction were reduced. There was no change in cardiac output. Although both drugs caused evidence of depression of conductivity and contractility, these appeared at lower dosage and lower plasma concentrations with bupivacaine than with ropivacaine.(ABSTRACT TRUNCATED AT 250 WORDS)     

罗哌卡因与丁哌卡因硬膜外麻醉剖宫产的药效学比较

目的 将新型酰胺类局部麻醉药罗哌卡因的的药效学与丁哌卡因进行比较。方法 选择行择期剖宫产的产妇２０例,分成两组进行硬膜外麻醉。随机在硬膜外注入０．７５％罗哌卡因。对镇平面及达到最高平面和最低平面所用时间,运动阻滞程度及恢复时间,术中镇痛效果,新生儿Ａｐｇａｒ评分,不良反应的发生情况,血压和心率的变化进行观察。．