Levobupivacaine, the S(−) enantiomer of racemic bupivacaine, in strengths of 0.125 and 0.25%, has produced comparable efficacy with the same concentrations of racemic bupivacaine [1,2] in clinical practice. Lyons and colleagues used an up and down sequential allocation to determine the minimum local analgesic concentrations of epidural levobupivacaine and bupivacaine for pain relief during the first stage of labour; the potency ratio was about 1 . Ropivacaine is 40% less potent than bupivacaine [4,5]. These three local anaesthetic solutions have not yet been compared at equianalgesic concentrations.
The objective of this study was to compare the analgesic efficacy, delay and duration of analgesia, and the degree of motor block with epidural levobupivacaine, ropivacaine and bupivacaine given at equianalgesic concentrations during the first stage of labour in spontaneously labouring primiparae. We used levobupivacaine 0.0625%, ropivacaine 0.10% and bupivacaine 0.0625%, all with the addition of sufentanil 10 μg.
Our Hospital Ethics Committee approved the study, and written informed consent was obtained from all patients. We enrolled 129 healthy primigravida, in active labour, who requested epidural analgesia in this randomized, observer-blinded study. All the women had reached at least 36 weeks' gestation, presented a spontaneous onset of labour and were in their first stage of labour with cervical dilatation <5 cm. Women with any disorder of pregnancy, breech or multiple gestation or those who had received opioid analgesia or sedative medication were excluded from the study. Women requiring oxytocin before epidural analgesia and those scoring <50/100 on a visual analogue pain scale before epidural analgesia were also excluded.
A lumbar epidural catheter was inserted with the women in the left lateral position using a midline approach. The epidural space was located with a 16-G Tuohy needle at the L2-3 or L3-4 interspace using the loss of resistance technique. A multiorifice epidural catheter was advanced 3-4 cm. No test dose was given.
Using a computer-generated list, parturients were randomly allocated to receive either levobupivacaine 0.0625%, ropivacaine 0.10% or bupivacaine 0.0625%. In all parturients, sufentanil 10 μg was added to the local anaesthetic; the total volume of solution was 20 mL. Each study solution was freshly prepared by an anaesthetist not directly involved in the patients' care or data collection; physiological saline was added to achieve the desired concentration. Completion of the epidural injection was regarded as time zero.
Pain was evaluated at the peak of each contraction using a 100 mm visual analogue scale (where 0 = no pain and 100 = worst possible pain). Assessment was performed immediately before the epidural block and at 5, 10, 15, 20 and 30 min thereafter from the completion of the injection. Analgesia was considered to be adequate if the visual analogue scale was <20 at 30 min. If pain relief was not satisfactory (visual analogue scale >20) at 30 min, an additional bolus was injected through the epidural catheter and the parturient was excluded from further evaluation.
Parturients were monitored with a non-invasive blood pressure cuff and pulse oximetry before the epidural block, and every 5 min thereafter for the first 30 min. Hypotension - defined as a decrease in baseline systolic arterial pressure ≥ 20 mmHg or a systolic arterial pressure < 90 mmHg - was treated by turning the patients into the left lateral decubitus position and by administration of intravenous fluids or ephedrine as necessary. Fetal heart rate monitoring and tococardiography was started at least 20 min before the epidural block. Subsequently, continuous or intermittent monitoring was performed at the discretion of the obstetric care team.
Maternal motor block and motor function were assessed only if satisfactory analgesia was achieved at 30 min. Motor block was evaluated using a modified Bromage score, where 4 = no block (full flexion of knees and feet possible); 3 = partial block (able to flex knees, full flexion of feet still possible); 2 = almost complete block (unable to flex knees but flexion of feet still possible); and 1 = complete block (unable to move legs and feet). The adequacy of motor function for walking was evaluated using the following criteria: sitting on the edge of the bed, standing unassisted, performance of a deep knee bend and a negative Romberg's test. Ambulation was considered possible after three unassisted steps.
Delay of analgesia was considered to be the interval from the completion of the injection of drug to the first painless contraction (visual analogue scale ≤20). The duration of analgesia was the time from the first painless contraction to parturients' request for pain relief.
Patients' characteristics and obstetric data are presented as mean (±SD), median (range) and count (percentage) as appropriate, and are analysed using the analysis of variance or Kruskal-Wallis nonparametric ANOVA tests. P < 0.05 was considered as statistically significant.
The randomization process allocated 43 parturients to the levobupivacaine group, 45 to the ropivacaine group and 41 to the bupivacaine group. Five parturients in the levobupivacaine group, four in the ropivacaine group and three in the bupivacaine group were excluded because of protocol violations. Four parturients in the levobupivacaine group, four in the ropivacaine group and three in the bupivacaine group complained of inadequate analgesia (P > 0.05); they required an additional epidural analgesic bolus and were excluded from further analysis. Eventually, data from 34 parturients in the levobupivacaine group, 37 in the ropivacaine group and 35 in the bupivacaine group were analysed (Table 1). There were no differences in patients' characteristics, initial labour characteristics or intensity of pain before the onset of epidural analgesia between the three groups.
There were no significant differences in the delay of analgesia, the degree of motor blockade and the number of parturients who could walk. Levobupivacaine and ropivacaine produced more prolonged analgesia than bupivacaine (P < 0.01) (Table 2). We did not observe any changes in fetal heart rate. There were no cases of maternal hypotension after the institution of the epidural block.
A post hoc power calculation revealed an 80% power (type I error = 0.05) of the study to detect a 25 min difference in the duration of analgesia.
These low concentrations of epidural levobupivacaine, ropivacaine and bupivacaine with the addition of sufentanil 10 μg were similar in terms of the quality of analgesia and motor block during the first stage of labour. However, levobupivacaine and ropivacaine produced a longer lasting analgesic effect compared with bupivacaine.
Burke and colleagues compared levobupivacaine 0.25% with bupivacaine 0.25% for epidural analgesia in labour: levobupivacaine and bupivacaine were equivalent in terms of onset time, quality and duration of analgesia, and induced comparable motor blockade . Another study compared continuous epidural infusions of levobupivacaine 0.125% and bupivacaine 0.125%: the two drugs were equally effective with regard to analgesia and motor blockade, although there was a trend toward less motor block in patients receiving levobupivacaine .
A number of studies have compared the analgesic efficacy, for epidural pain relief during labour, of bupivacaine and ropivacaine at a concentration of 0.25 or 0.125% [6-9]; however, no differences in the quality of analgesia or motor blockade were demonstrated. In contrast to these findings, comparisons of bupivacaine 0.125% with ropivacaine 0.125%, in combination with opioids, for epidural labour analgesia revealed no differences in the quality of analgesia, although ropivacaine produced less motor blockade [10,11].
Comparable analgesia between ropivacaine and bupivacaine at the same concentrations seems to be because the doses of these local anaesthetics were at the top of the dose-response curve, and therefore, were supratherapeutic . Capogna and colleagues  and Polley and colleagues  calculated the relative analgesic potencies of bupivacaine and ropivacaine by using an up-down sequential allocation study design. They concluded that ropivacaine was significantly less potent than bupivacaine, with a potency ratio of 0.6. Only with the use of equivalent local anaesthetic concentrations can the analgesic efficacy and motor block be evaluated properly. A recent study of analgesia during labour compared continuous infusions of epidural bupivacaine and ropivacaine at concentrations thought to be equipotent. The authors concluded that 0.0625% bupivacaine and ropivacaine 0.1% were equally effective in terms of pain relief, level of sensory anaesthesia, degree of motor block and patient satisfaction .
This is the first study that compares levobupivacaine, ropivacaine and bupivacaine at equivalent low concentrations. Although we did not use a continuous epidural infusion, we compared the effects, using a bolus dose, of three different local anaesthetic solutions and thus we were able to evaluate the duration of action of the study drugs. We found a longer lasting duration of analgesia with levobupivacaine and ropivacaine compared with bupivacaine. In contrast to our results, Burke and colleagues  found levobupivacaine 0.25% to have the same analgesic duration as bupivacaine 0.25%. The reason for this different finding maybe due to vasoactivity properties of levobupivacaine and ropivacaine. S(−) enantiomers such as levobupivacaine and ropivacaine produce a more pronounced vasoconstrictor effect than bupivacaine, and the difference is more pronounced at low concentrations [14,15]. We may speculate that this vasoconstrictor activity produced the longer duration of analgesia with levobupivacaine and ropivacaine.
The potency ratio between levobupivacaine and bupivacaine was estimated at 0.98 in weight/volume terms and 0.87 in molar terms . Because levobupivacaine is expressed as a free base, it has 11% more molecules than the equivalent percentage weight/volume of the racemate bupivacaine . The amount of free base determines the speed of onset of a local anaesthetic drug, but duration is determined by both the amounts of the free base and the ionized form. Further investigation is needed to establish whether this additional small amount of free base contributes to the longer duration of analgesia of levobupivacaine.
Since our study evaluated only the effects of the initial bolus dose, we were unable to determine if the longer duration of analgesia observed with levobupivacaine and ropivacaine was useful in reducing the total dose required during labour. With all three local anaesthetic regimens, about 10% of the parturients had inadequate analgesia. In addition, when using a continuous epidural infusion during labour, the advantages of a 25 min longer duration of analgesia remains to be substantiated.
In conclusion, we have demonstrated that equipotent low concentrations of epidural levobupivacaine, ropivacaine and bupivacaine, when added to sufentanil 10 μg, produced similar pain relief and motor block. Levobupivacaine and ropivacaine produced a longer lasting analgesic effect.
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