Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 4  |  Page : 585-593

Does levobupivacaine have a benefit over bupivacaine in our practice?


1 Department of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Anaesthesia and Intensive Care, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

Date of Submission15-Jan-2014
Date of Acceptance15-Mar-2014
Date of Web Publication29-Dec-2015

Correspondence Address:
Sawsan G Mohamed
Department of Anesthesiology and Intensive Care, Faculty of Medicine for Girls, Al-Azhar University, Cairo 11835
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.172746

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  Abstract 

Background
The well-known toxic effects of bupivacaine on central nervous system and cardiovascular system were a base for the development of new long-acting local anesthetics. Levobupivacaine is the pure S(-)-enantiomer of racemic bupivacaine. This study compares the efficacy of levobupivacaine as against bupivacaine by epidural clinical study and by different routes in animal study.
Materials and methods
Evaluation of the analgesic activities by the hot plate method was carried out in nine groups of mice. Each four groups were injected intraperitoneally with either levobupivacaine or bupivacaine. The control group received saline. The hemodynamic effects of levobupivacaine and bupivacaine were carried out on the isolated rabbit's heart and anesthetized cats for carotid blood pressure and ECG. Thirty patients undergoing limb surgery were randomized to receive 15 ml of 0.5% levobupivacaine or bupivacaine through epidural needle. Intraoperative blood pressure and heart rate were recorded. Onset time of sensory and motor block, time to T10 sensory block, complete motor block, quality of analgesia, and times for two segment regressions were detected.
Results
Experimentally, the intensity and duration of analgesia produced by levobupivacaine was more than that of bupivacaine. Both drugs induced significant dose-dependent negative inotropic effect, but it was lesser in levobupivacaine than in bupivacaine. An amount of 2 mg/kg levobupivacaine produced a significant rise in blood pressure and 4 mg/kg significantly decreased it, whereas 1 and 2 mg/kg bupivacaine produced a significant decrease in blood pressure. The ECG pattern of levobupivacaine showed no abnormalities, but bupivacaine at a dose of 2 mg/kg produced significant bradycardia and ECG changes. Cardiac arrest and death of cats occurred when 4 mg/kg of bupivacaine was injected. Clinically, the onset time of sensory block, time to T 10 sensory block and time to complete motor block are lower with bupivacaine than with levobupivacaine.
Conclusion
We found, based on the current pharmacodynamics evidence from this experimental and clinical study, that levobupivacaine has good analgesic activity and less cardiodepressant effect, and it offers advantages over bupivacaine.

Keywords: bupivacaine, epidural anesthesia, levobupivacaine, new local anesthetics


How to cite this article:
EL-Din SB, Mohamed SG, Ghoneim SH. Does levobupivacaine have a benefit over bupivacaine in our practice?. Ain-Shams J Anaesthesiol 2015;8:585-93

How to cite this URL:
EL-Din SB, Mohamed SG, Ghoneim SH. Does levobupivacaine have a benefit over bupivacaine in our practice?. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2019 Sep 15];8:585-93. Available from: http://www.asja.eg.net/text.asp?2015/8/4/585/172746


  Introduction Top


Regional anesthesia, particularly peripheral nerve blockade, is useful for orthopedic patients. These techniques are often used to provide not only anesthesia, but also postoperative analgesia after limb surgery [1] .

Bupivacaine is a long-acting amide and is widely used as local anesthetic (LA) for epidural anesthesia. It has a beneficial ratio of sensory to motor block in epidural anesthesia. This agent provides also high quality analgesia during the postoperative period. However, bupivacaine-induced cardiotoxicity in patients following accidental intravascular injection limits its use [2] .

The well-known toxic effects of bupivacaine on the central nervous system and on the cardiovascular system were a base for the development of new long-acting LAs, such as ropivacaine and levobupivacaine, to present a safer alternative to bupivacaine [3] .

Bupivacaine is used as a racemic mixture of equimolar amounts of R(+)-bupivacaine and S(-)-bupivacaine. R(+)-bupivacaine is found more toxic to both the central nervous system and the cardiovascular system. Levobupivacaine (S-1-butyl-2-piperidylformo-2΄, 6΄-xylididehydrochloride) is the pure S(-)-enantiomer of racemic bupivacaine. Preclinical animal and volunteer studies showed less cardiac toxicity than bupivacaine. It seems to be an alternative LA agent in epidural anesthesia [2] .

LAs inhibit the sodium channels on neural membranes. Therefore, they cause a loss of conduction on neural structure and a loss of sensorial innervation. Systemic toxicity occurs as a result of excessive blood levels of LAs in the central nervous and cardiovascular systems when they are injected intravenously by mistake. They cause direct negative inotropic effect, myocardial conduction abnormalities, and arrhythmias. Arrhythmogenic effects of these drugs are related to repolarization of potassium, sodium, and calcium channels. Consequently, with this mechanism, cardiac impulse conduction slows down, QRS complex widens, PR distance gets longer, atrioventricular block occurs, and fatal ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation occurs [2] .

The aim of this prospective randomized double-blinded study was to compare the efficacy and safety of 0.5% levobupivacaine with a 0.5% racemic mixture of bupivacaine by epidural clinical study and by different routes in animal study.


  Materials and methods Top


Experimental study

All animals were housed at the animal house in the Faculty of Medicine for Girls, Al-Azhar University between the periods of October 2012 and April 2013. Doses used in this work, corresponding to the human therapeutic doses, were calculated according to the method given by Paget and Barnes [4] .

Evaluation of the analgesic activities

Hot plate method by Ghosh
[5] : Nine groups of 10 mice in each group (of both sexes and weighing 20-25 g) were used. Four groups were injected intraperitoneally with 1.75-14 mg/kg levobupivacaine, whereas another four groups were given 1.75-14 mg/kg bupivacaine. The last group received saline and was used as a control. After 2 h from drug injection, each mouse of all groups was placed separately on a hot plate (55°C) and the time needed for leaking the mouse hind limbs was recorded.

Evaluation of the hemodynamic effects

Experiments on the isolated mammalian heart of rabbit (The Staff of the Department of Pharmacology University of Edinburgh
[6] : Six rabbits of both sexes with an average weight of 1-2 kg were used. The effect of different doses of levobupivacaine (2-16 mg/ml) and bupivacaine (2-16 mg/ml) was studied on the amplitude of myocardial contractions by injecting the drug into the perfusion fluid through the rubber tube proximal to the heart.

Experiments on the carotid arterial blood pressure and ECG of pentobarbitone-anesthetized intact cats (The Staff of the Department of Pharmacology University of Edinburgh [7] : Six cats of both sexes with an average weight of 2-3 kg were used. The effect of intravenous injection of different doses of levobupivacaine (0.5-4 mg/kg) and bupivacaine (0.5-4 mg/kg) on the arterial blood pressure and ECG (lead II) of pentobarbitone-anesthetized intact cats was recorded.

Clinical study

After obtaining local ethical committee approval, 30 patients, ASA physical status I-II, aged from 20 to 55 years old, undergoing elective limb surgery were included in this prospective, randomized, double-blind study. This study was conducted in Al-Zahraa University Hospital between the period of April 2012 and November 2012. Exclusion criteria included patients who had any contraindications to epidural anesthesia, patients refusing regional anesthesia, allergy to LA solutions, clotting abnormalities, and history of drug abuse. In addition, patients with diabetes, any neurologic, cardiopulmonary, or psychiatric disease, those receiving antiarrhythmic/beta blockers/anticoagulants, and pregnant women were excluded from the study.

All patients were approached on the morning of their operation to explain the procedure, advantage, and possible side effects before informed written patient consent was obtained and to instruct the patients about usage of the visual analog scales (VAS) for assessing pain. In the operation theater, a peripheral intravenous cannula was inserted and all patients received 500 ml of Ringers lactate solution for volume expansion before the epidural block.

Standard monitoring was conducted and the basal heart rate (HR), noninvasive mean arterial blood pressure (MABP), ECG (five leads), and peripheral oxygen saturation (SpaO 2 ) were recorded. A nasal cannula was applied and supplemental oxygen was given throughout the procedure at 4 l/min.

The patients were randomized into two groups according to the LA solution used. Group L (n = 15) received 15 ml of 0.5% levobupivacaine and group B (n = 15) received 15 ml of 0.5% bupivacaine through epidural Tuohy needle (B. Braun Melsungen AG, 34209 Melsungen, Germany). The L2-3 or L3-4 epidural space was identified with patients in the sitting or lateral decubitus position, and skin infiltration with 2 ml lignocaine 2% was performed. An 18 G Tuohy needle was inserted using the midline approach and a loss of resistance technique. After negative aspiration for blood or cerebrospinal fluid, a 3 ml of lignocaine with 1 : 200 000 adrenaline test dose was administered to exclude intravascular or intrathecal placement of the needle. Then after a 5-min period, the study drug was injected over 2 min. The anesthetists who performed the epidural catheterization and collected the data were blinded to the solutions used.

Standard monitoring was continued throughout the operation. Measurements of MABP, HR, and respiratory rate were recorded every 15 min. Hypotension was defined as a 30% decrease of systolic blood pressure compared with the baseline value; ephedrine bolus 5 mg was given intravenously as needed or if it was lower than 90 mmHg. An HR less than 50 beats/min was defined as bradycardia and treated with atropine 0.5 mg intravenously, and a decrease in SpaO 2 to less than 93% was defined as hypoxia and treated with supplemental oxygen by face mask.

Sensory and motor blocks were assessed by the pinprick test (1 = hypoalgesia, 2 = analgesia, 3 = analgesia plus hypoalgesia, and 4 = anesthesia) and modified Bromage scale (0 = no motor block, full flexion of hips, knees, and ankles, 1 = ability to move knees only, inability to raise extended legs, 2 = ability to move feet only, inability to flex knees, and 3 = full motor block, inability to flex ankle joints), respectively.

Level of analgesia to pinprick was assessed bilaterally every 5 min until complete loss of sensation at T10 (taken as onset of sensory block) and then every 5 min to determine the time taken for maximum height of block, and thereafter every 15 min to determine the time for two segment regression and regression of sensory block at T12 (taken as duration of sensory block).

Motor blockade was assessed according to the modified Bromage scale (0 = no motor block, 1 = inability to raise extended legs, 2 = inability to flex knees, and 3 = inability to flex ankle joints) at 5, 15, 30, and 60 min after the injection. The quality of analgesia, as defined by pain at the time of skin incision, was recorded as a 0-10 verbal numeric pain score where 0 is no pain and 10 is the worst imaginable pain. Recovery from motor block was assessed at the end of surgery.

Any complications such as nausea, vomiting, headache, tinnitus, confusion, convulsion, or hemodynamic variables (hypotension, hypertension, arrhythmias) were recorded and tabulated.

In the postanesthesia care unit, vital signs were recorded every 15 min for 2 h (unless there are complications, irrespective of the causes). All patients were asked to define hourly their degree of pain during 24 h postoperatively by means of VAS ranging from 0 to 10 (0 = no pain and 10 = worst pain). Eventual rescue analgesia was obtained by additional doses of paracetamol (500-1000 mg) in case of VAS greater than 4.

Statistical analysis

Sample size was calculated using Epi info statistical program version 7 (Centers for Disease Control and Prevention (CDC), 1600 Clifton Road Atlanta, Georgia, USA) by adjusting power of the test to 80%, confidence interval to 95%, and margin of error accepted to 5%. The data were collected, revised, and entered to the statistical package for social science, version 17 (International Business Machines Corp. (IBM), 233 South Wacker Drive, Chicago, USA). The quantitative data were presented as mean, SDs, and SEM, whereas the qualitative data were presented as number and percentages. The independent t-test was used to assess the significant difference between two independent groups with parametric data, and the paired t-test was used to assess the significant difference between two paired groups with parametric data, whereas the c2 -test was used to assess the significant difference between groups with qualitative data and the Fisher exact was used instead of the c2 -test when the expected count in any cell was found less than 5. The P-value was considered significant at the level of less than 0.05 and considered highly significant at the level of less than 0.01.


  Results Top


Experimental study

Evaluation of the analgesic activities

Hot plate method
: In this test, the analgesic activity of different doses of levobupivacaine showed a highly significant analgesic effect in comparison with bupivacaine [Table 1] and [Figure 1].
Figure 1: Percentage activity of the reaction time in the hot plate test by levobupivacaine and bupivacaine

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Table 1 Mean reaction time (s) to the stimulus of hot plate test of mice treated (intraperitoneally) by different doses of levobupivacaine or bupivacaine and of control untreated mice

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Evaluation of the hemodynamic effects

Experiments on the isolated mammalian heart of rabbit
: Levobupivacaine (2-16 mg/ml) reduced the myocardial contractility significantly by 8.036 ± 0.821 and up to 44.515 ± 0.886% (P < 0.001), whereas bupivacaine (2-16 mg/ml) decreased it significantly by 17.105 ± 0.915 and up to 82.447 ± 0.988% (P < 0.001) [Table 2] and [Figure 2] and [Figure 3].
Figure 2: Effect of levobupivacaine on the amplitude of myocardial contractions of isolated rabbit's heart

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Figure 3: Effect of bupivacaine on the amplitude of myocardial contractions of isolated rabbit's heart

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Table 2 Percentage reduction in the amplitude of contractions (cm) of isolated rabbit's heart in response to different doses of levobupivacaine and bupivacaine (¦Ìg/ml)

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Experiments on the carotid arterial blood pressure and ECG of pentobarbitone-anesthetized intact cats: Levobupivacaine at doses of 0.5 and 1 mg/kg produced insignificant rise in MABP. The drug at a dose of 2 mg/kg produced significant rise in MABP, whereas the last dose of the drug (4 mg/kg) significantly decreased blood pressure [Table 3] and [Figure 4].
Figure 4: Effect of levobupivacaine on the mean blood pressure of normal anesthetized intact cat

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Table 3 Percentage change in the mean arterial blood pressure (mmHg) of pentobarbitone-anesthetized intact cats in response to different doses of levobupivacaine and bupivacaine (mg/kg)

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However, bupivacaine at a dose of 0.5 mg/kg produced insignificant rise in the MABP, whereas at doses of 1 and 2 mg/kg it produced significant decrease in MABP. The animals died after being injected with the last dose of bupivacaine (4 mg/kg) [Table 3] and [Figure 5].
Figure 5: Effect of bupivacaine on the mean blood pressure of normal anesthetized intact cat

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With respect to the ECG, no abnormality in the ECG pattern was observed with levobupivacaine and the first two doses of bupivacaine. Concerning the effect of 2 mg/kg bupivacaine, there was a significant decrease in the HR and ECG changes in form of depression of ST segment, widening of QRS complex, decreased QRS voltage, and prolongation of PR interval, finally ending with cardiac arrest and death of cats when the last dose of bupivacaine was injected [Table 4].
Table 4 Percentage reduction in the heart rate (beats/min) of pentobarbitone-anesthetized intact cats in response to different doses of levobupivacaine and bupivacaine (mg/kg)

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Clinical study

A total of 30 patients, ASA physical status I-II were randomized into two groups according to the LA solution used. Group L (n = 15) received 15 ml of 0.5% levobupivacaine and group B received 15 ml of 0.5% bupivacaine through epidural Tuohy needle into the epidural space.

Patient's age, sex, and weight and duration of surgery were comparable, and there were no statistically significant differences between the two groups [Table 5].
Table 5 Demographic variables and duration of surgery (min)

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There were no statistically significant differences between two groups for the HR and MABP in the first hour and all over the duration of surgery (P > 0.05) [Table 6] and [Table 7].
Table 6 Heart rate changes before and after epidural injection of studied drugs

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Table 7 MABP changes before and after epidural injection of studied drugs

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There were high statistically significant differences between the L and B groups with respect to the onset time of sensory block (19.5 ± 0.79 vs. 16.5 ± 0.85 min) and time to T10 sensory block (29 ± 2.0 vs. 25 ± 0.8 min). In addition, the time to complete motor block in the L group was more than the time in the B group (30.4 ± 3.0 vs. 28.6 ± 2.0 min) with P equal to 0.05, which is statistically significant [Table 8] and [Figure 6].
Figure 6: Onset time and time to T10 of sensory block in both groups

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Table 8 Parameters of epidural anesthesia in both groups

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There were no statistically significant differences between the two groups in onset time of motor block and the quality of analgesia. Although the mean times for two segment regression and recovery from motor block were shorter in the L group, there was no statistically significant difference [Table 8].

In the postanesthesia care unit, there were no statistically significant differences between the two groups in the HR and MABP, and none of the patients in both groups required supplement analgesics for 2 h postoperatively, where VAS was greater than 4.


  Discussion Top


Regional anesthesia might require high doses of LA agents for surgery, and there is always the potential risk for toxic reactions. Both the cardiovascular and central nervous systems are the primary target organs of LA toxicity with accidental intravascular injection. Bupivacaine was one of the most widely used LAs because of its quality of anesthesia and prolonged duration of action [8] .

Levobupivacaine is the pure S(-)-enantiomer of racemic bupivacaine; preclinical animal and volunteer studies showed less cardiac toxicity than bupivacaine. It seems to be an alternative LA agent in epidural anesthesia [9],[10] .

Concerning the analgesic activity of levobupivacaine and bupivacaine, the experimental result in the present study showed that the analgesia produced by levobupivacaine was rapid onset and long duration than that of bupivacaine; levobupivacaine prolonged the reaction time to the stimulus of hot plate test more than bupivacaine; however, in the clinical study, we found that the onset time of sensory block, time to T10 sensory block, and time to complete motor block are lower with bupivacaine than with levobupivacaine, and there was no statistical difference in the onset time of motor block and the quality of analgesia between both drugs. Although the mean times for two segment regression and recovery from motor block are shorter in the L group, there is no statistically significant difference; these discrepancies between experimental and clinical results may be due to animal to human variation and the route of administration.

Levobupivacaine is currently the closest to the ideal agent for neural blockade. The onset of sensory and motor block is related to the physicochemical properties of the individual drugs, namely the mass of the injected LA, the pKa of the drug, and pH of the tissues [11] .

In contrast to our results, Glaser et al. [9] , Uzuner et al. [2] , and Bergamaschi et al. [12] reported that levobupivacaine and bupivacaine have similar efficiency, but levobupivacaine has a greater degree of separation between motor and sensory blockade than bupivacaine when it is given for epidural pain relief during labor. In addition, Kopacz et al. [13] compared 0.75% levobupivacaine and bupivacaine for epidural anesthesia in lower abdominal surgery and observed similar onset times but a significantly longer duration of sensory blockade when levobupivacaine was used. However, a significant difference was observed, where complete regression occurred 45 min sooner with bupivacaine and slower onset of lower extremity motor block occurred with levobupivacaine. Overall, the duration of lower extremity motor block was similar for patients administered levobupivacaine and bupivacaine. The overall quality of sensory and motor blocks as assessed by the investigator was 'excellent' or 'good' in 96% of patients in the levobupivacaine group and 82% of patients in the bupivacaine group. No serious adverse events were related to study medication. In agreement with clinical results, Arslantas et al. [14] found no difference as to motor block development between the groups, but the sensory block was monitored less in group L at 15, 30, 45, and 90 min. In addition, Foster and Markham [15] have shown that the sensory blockade lasted significantly longer with levobupivacaine than with racemic bupivacaine, which might be attributable to a greater intrinsic vasoconstrictor potency of levobupivacaine.

The analgesic activities result from direct block of transmission of pain from nociceptive afferents. LA agents are applied directly, and their efficacy results from action on the nerve where the inward Na + current is blocked at the sodium ionophore during depolarization. LAs not only block Na + channels, but also Ca 2+ and K + channels [16] , transient receptor potential vanniloid-1 receptors [17] , and other ligand-gated receptors. LAs also disrupt the coupling between certain G proteins and their associated receptors, in addition to a variety of other antithrombotic and neuroprotective actions of intravenous LAs [18] . Through this action, LAs exert potent anti-inflammatory effects, particularly on the neutrophil priming reactions [19] .

With respect to the cardiovascular experiments in this study, levobupivacaine and bupivacaine at all concentrations exerted a significant negative inotropic effect on the isolated perfused rabbit heart. The myocardial depressant action of bupivacaine was found greater than that of levobupivacaine and the last dose of bupivacaine (16 ug/ml) caused 82.447% reduction. Such finding was in agreement with the studies by Nau et al. [20] and Heavner [21] who stated that levobupivacaine was less potent in depressing cardiac electrophysiological parameters than bupivacaine in an isolated heart model, with levobupivacaine being the least toxic than that of bupivacaine.

In-vitro studies indicate that, with levobupivacaine [S(-) bupivacaine], there is less sodium channel blockade, faster unblocking of sodium channels, and a marked decrease in potassium blockade compared with racemic bupivacaine [22] and that, as a result, levobupivacaine is less cardiotoxic. In a further study to explore the effects of larger doses in sheep, the mean fatal dose for levobupivacaine was found to be 277 mg compared with 156 mg for bupivacaine [23] .

Butterworth [24] and Mio et al. [25] attributed the potent cardiodepressant activity of bupivacaine compared with that of levobupivacaine for its slow release from Na + channel-binding sites as well as Ca + channel-binding sites. Similarly, Punke and Friederich [26] suggested that binding of bupivacaine more than levobupivacaine with the dihydropyridine-binding sites on neuronal L-type of Ca + channels may be involved in the cardiotoxicity. Bupivacaine has also been shown to inhibit carnitine-acylcarnitine transferase in rat cardiac interfibrillar mitochondria. Carnitine-acylcarnitine transferase is the only enzyme responsible for transporting acylcarnitines across the mitochondrial membranes in the fatty acid transport chain during phase I mitochondrial respiration important for aerobic metabolism [27] ; this may be a key factor in the nature of LA-induced toxicity being unresponsive to advanced cardiac resuscitation techniques.

Apart from the channel blockade, the membrane interaction (especially with cardiac mitochondria) that modifies membrane biophysical properties such as fluidity, ordering, and permeability is altered by cardiotoxic drugs. Bupivacaine affects and rapidly reach mitochondrial membranes of cardiomyocytes even when applied extracellularly by its action on membrane cardiolipin [28],[29],[30] . Ngamprasertwong et al. [31] and Tsuchiya et al. [32] reported that the high lipophilicity and protein binding of bupivacaine may favor enhanced uptake and binding in the myocardial tissue, making cardiac resuscitation more difficult following bupivacaine-induced cardiovascular collapse.

In experiments on the arterial blood pressure and ECG of pentobarbitone-anesthetized intact cats, in accordance to our results, De La Coussaye et al. [33] and Lefrant et al. [34] have revealed bupivacaine as a negative inotropic agent, with intravenous infusions causing significant decreases in blood pressure and HR through alterations in electrical excitability of the heart, dilatation of blood vessels, and inhibition of the firing rate of the sinoatrial node. Typical effects on the ECG include widening of the QRS complex and lengthening of the PR interval.

Hypotension that occurred in the cats injected with 4 mg/kg of levobupivacaine in the present study might be explained by achievement of high blood level of the drug in these animals leading to myocardial depression. Animal variability, with respect to the rate of absorption, metabolism, and excretion of the injected drug, as well as the way of injection may influence the blood level, and accordingly toxicity of the drug. If the blood level of LA is excessively elevated, cardiovascular depression occurs, which is related to its depressant effect on myocardial contractility and HR [35] .

In contrast to the vasopressor effect of levobupivacaine in this study, small doses of bupivacaine, in general, elicited insignificant effect on blood pressure, whereas larger doses, which increased drug blood level, produced hypotension. When the blood level of bupivacaine became highly elevated in some cats, severe hypotension and death of the cats occurred. This result is in accordance with the studies by Jung et al. [36] and Groban et al. [37] who speculated that the primary cause of cardiovascular collapse induced by bupivacaine may be due to hypotension from diminished contractility rather than arrhythmias in anesthetized dogs.

As levobupivacaine has less potential for sodium channel blockade and produces less arrhythmias, it has been a popular LA agent [38] . It was thought that it can be used instead of bupivacaine because of its less toxic side effects to the cardiovascular and central nervous system [39],[40] . Corrected QT is used to evaluate the arrhythmogenic potential of drugs. Levobupivacaine has also a poor influence on QRS or corrected QT [41] .

The present clinical study demonstrates that the epidural administration of 15 ml of 0.5% levobupivacaine or racemic bupivacaine in patients undergoing elective limb surgeries provides no statistically significant differences between the two groups for HR and MABP all over the duration of surgery.

Our hemodynamic results are comparable with the results of Uzuner et al. [2] and Arslantas et al. [14] , and contradicted with the results of Kopacz et al. [13] . Uzuner et al. and Arslantas et al. compared the epidural levobupivacaine and bupivacaine in major abdominal surgeries and labor analgesia, respectively, and there were no significant differences in systolic and diastolic pressures or in HR values between the groups. However, Kopacz et al. [13] found that hypotension was the most common side effect attributed to the study drug, and there were no differences between the groups with respect to change from baseline in HR, and there were no clinically significant ECG changes related to either study drug. This study demonstrates that 0.75% levobupivacaine is a suitable anesthetic for use in lower abdominal surgery. In addition, Bergamaschi et al. [12] demonstrated that the most frequent complication was hypotension, found in 66.7% of the levobupivacaine group patients and in 43.5% of the bupivacaine group patients. However, Ngamprasertwong et al. [31] found that hypotension was attributed to both study drugs, 38.7% in the levobupivacaine group compared with 66.7% in the bupivacaine group. Although there are no adverse effect in our clinical study, the other studies observed complications such as nausea, vomiting, agitation, ventricular premature complexes (bigeminy), dyspnea, pruritus, [12],[31] and bradycardia [12] . Uzuner et al. [2] detected a higher incidence for supraventricular arrhythmia with bupivacaine during the postoperative period.

Finally, based on these results, the current pharmacodynamic evidence from animal and human studies suggests that levobupivacaine has good analgesic activity and less cardiodepressant effect, and it offers advantages over the racemic bupivacaine.


  Acknowledgements Top


Conflicts of interest

None declared.

 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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