The mean total amount of epidurally administered medication was 38.9 ± 18 mL (48.6 ± 23 mg bupivacaine) in G1, 41.7 ± 30 mL (52.1 ± 38 mg ropivacaine) in G2, 34.7 ± 19 mL (60.7 ± 33 mg ropivacaine) in G3 and 40.1 ± 17 mL (80.2 ± 34 mg ropivacaine) in G4. Due to the higher local anaesthetic concentration the amount of local anaesthetics used in G4 was significantly increased compared to G1-G3 (P < 0.05). The incidence of side-effects was similar in all four groups except for pruritus, which was significantly less frequent in the group treated with ropivacaine 0.2% without sufentanil (Table 3).
Patients included in the analysis of motor function are depicted in Figure 3. Modified Bromage scores were comparable for G1, G2 and G3. G4 had a significantly higher incidence of motor blockade after 2 h (Table 4), although the average score in this group did not exceed 1. Strength of the abdominal muscles, as assessed by the RAM-test, did not decrease after initiation of epidural analgesia and did not differ between groups (Table 5).
There were no differences in the duration of the first or second stage of labour. Moreover, the incidence of instrumental deliveries and Caesarean sections was identical in all groups (Table 6).
The results of the present multicentre trial demonstrate a comparable analgesic efficacy of ropivacaine 0.125% and bupivacaine 0.125% combined with sufentanil, while ropivacaine 0.175% proved slightly superior in the initiation of labour analgesia without enhancing motor blockade. The two local anaesthetics, thus, appeared clinically indistinguishable.
Ropivacaine has been shown to produce less toxicity and motor blockade compared to bupivacaine in equal concentrations [1,2], indicating a superior safety profile when used for regional anaesthesia. These advantages of ropivacaine have been challenged by Capogna and colleagues  and Polley and colleagues , who demonstrated a difference in analgesic potency between ropivacaine and bupivacaine with a potency ratio of 0.6 using the up-down sequential allocation method. These authors also suggested that previous studies comparing both local anaesthetics applied concentrations that were too high and well beyond the steep part of the dose-response curve to detect significant differences. In support of the different potencies Fernández-Guisasola and colleagues  reported a similar analgesic effect of continuous infusions of bupivacaine 0.0625% and ropivacaine 0.1% in the presence of fentanyl.
Although the determination of minimal local anaesthetic concentration (MLAC) has undoubtedly added valuable information to our current understanding of local anaesthetics, there are several caveats when applying these results to the clinical situation throughout labour. First, they only evaluate the concentration necessary for the initiation of labour analgesia as opposed to doses necessary throughout labour and delivery. Second, reported effective concentrations to obtain analgesia in 50% of patients (EC50) merely represent one point of the dose-response curve. They do not predict whether the slopes of the dose-response curves of the two drugs are identical or whether they overlap at higher and clinically more relevant concentrations (e.g. the EC95). Third, the EC50 is determined with a VAS score below 10 mm defined as successful analgesia. Clinically, VAS scores below 20-30 mm are considered sufficient and are in the range that parturients choose, when using a PCEA device. The EC50 determined in MLAC studies may, therefore, not be identical to the EC50 to obtain a VAS score <30 mm. Fourth, the up-down sequential allocation method focuses on the concentration of the local anaesthetic given in a large dilute volume. This focus on concentration rather than on dose may have distorted the interpretation of previous studies and has led to new studies comparing lower concentrations closer to the EC50. However, several studies have shown that the intensity of sensory and motor blockade is dependent on total local anaesthetic dose rather than concentration [18-20], and studies should not be refuted based on concentration alone.
In the present study, local anaesthetic concentrations were high and well above the respective EC50, but total doses throughout labour and delivery were low. On a milligram basis, the initial dose of ropivacaine 10 mL 0.175% (17.5 mg) plus sufentanil (7.5 μg) in the present study did not contain more ropivacaine than the EC50 of ropivacaine in the presence of sufentanil (ropivacaine 20 mL 0.09%; or 18 mg) , although Palm and colleagues used twice the dose of sufentanil (15 μg). However, this dose provided satisfactory analgesia in 89% of patients in the present study, and underscores the fact that the EC50 required to obtain a VAS score <10 mm is different from that to obtain a VAS score <30 mm. Similarly, our concentration of bupivacaine and sufentanil appear to be high, since Polley and colleagues  determined the EC50 of bupivacaine in the presence of sufentanil 0.5 μg mL−1 to be 0.048%, but again - in terms of total milligrams of bupivacaine and sufentanil applied - these doses are rather similar (e.g. bupivacaine 9.6 mg plus sufentanil 10 μg vs. bupivacaine 12.5 mg plus sufentanil 7.5 μg in the present study). Again, the low doses of bupivacaine and sufentanil applied in the present study provided satisfactory analgesia in 87% of patients. The dose of sufentanil added to local anaesthetics has been previously demonstrated to be the optimal dose  and is below the doses of sufentanil reported by Polley and colleagues . Although the addition of sufentanil may have masked differences between the two local anaesthetics in terms of potency, sufentanil would have prolonged the duration of the epidural solution in an identical fashion in all opioid groups, and thus, does not confound the present results. Moreover, the addition of potent opioids represents current standard and the results are, therefore, applicable to clinical practice. The low doses of opioids used would not suffice to provide efficient analgesia without the concurrent addition of local anaesthetics.
The interpretation of previous results may additionally be confounded by the mode of application of the local anaesthetic solution. Finegold and colleagues  recently demonstrated a similar analgesic efficacy of ropivacaine 0.1% compared to bupivacaine 0.125%, using continuous infusions. However, continuous infusions increase total overall local anaesthetic doses and may have masked any true differences between the two drugs.
If local anaesthetics are delivered on demand only via intermittent top-up boluses or a PCEA device, differences in potencies should lead to higher local anaesthetic requirements in patients treated with ropivacaine. Gautier and colleagues  used intermittent top-up boluses and showed similar analgesic efficacy of ropivacaine 0.125% and bupivacaine 0.125%, whereas bupivacaine 0.1% increased the number of boluses needed to provide effective analgesia, indicating that both drugs are equally effective when used in identical concentrations. Similarly, we did not observe any differences in PCEA requirements between the two drugs.
Fischer and colleagues  and Meister and colleagues  used a PCEA technique and demonstrated a similar analgesic effect of ropivacaine and bupivacaine in equal concentrations without differences in local anaesthetic consumption. In the latter study, ropivacaine produced less motor blockade than bupivacaine, which may have resulted from the addition of a background infusion. Total doses applied were much higher than in the present study using a bolus-only mode, and may have only been below the threshold for producing motor blockade with ropivacaine but not with bupivacaine. In a subsequent study, the same group was unable to demonstrate any differences in analgesic quality or motor blockade between ropivacaine 0.075% and bupivacaine 0.075% , although total doses of local anaesthetics were still higher than in the present study. We included the RAM-test to enhance the sensitivity of testing motor strength, which may be more relevant to test the expulsive forces generated in the second stage of labour. We were, nevertheless, unable to detect any significant differences in motor blockade.
Our study, thus, confirms that ropivacaine and bupivacaine are clinically equivalent in providing labour analgesia and suggests that the slope and shape of the dose-response curves of the two drugs may be closer together at the high end of the dose-response curve than derived from the up-down sequential allocation method. A 40% difference in potency of the EC50 may, therefore, not be extrapolated to a 40% difference of the EC95, until confirmed by traditional dose-response curves. The validity of applying an EC50 obtained from up-down sequential allocation to clinical endpoints has previously been questioned [27,28], and doses of ropivacaine for labour analgesia should not be increased based on these results alone. Our results also indicate that advantages of ropivacaine in terms of motor blockade are only apparent, if high doses of local anaesthetics independent of the concentration are used.
Advantages of ropivacaine in respect to toxicity are irrelevant in labour analgesia but may be of clinical importance for Caesarean section, provided that similar doses of both local anaesthetics can be administered. Datta and colleagues  demonstrated that equal doses of both local anaesthetics provide satisfactory anaesthesia with a comparable onset time, duration and spread of anaesthesia, but with a significantly shorter motor blockade after ropivacaine.
We did not observe any differences in instrumental deliveries and Caesarean sections. Although indications for instrumental deliveries and Caesarean sections were left to the discretion of the attending obstetrician, bias should be negligible with a study population of 411 patients, equally distributed among the different hospitals. In addition, Vertommen and colleagues  reported a similar incidence of Caesarean sections under epidural analgesia for two of the participating centres in 1991.
In summary, our data indicate that bupivacaine 0.125% and ropivacaine 0.125% in combination with sufentanil are equally effective in providing satisfactory labour analgesia. If analgesia is delivered with patient-controlled devices and without a background infusion, overall drug consumption appears to be below the threshold of inducing a significant motor blockade with both local anaesthetic drugs.
Funding: Department of Anaesthesiology and Intensive Care, Universitätsklinikum Münster, Germany. This study was presented in part at the 1999 Annual Meeting of the ASA, Dallas, Texas, USA.
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Keywords:© 2004 European Academy of Anaesthesiology
ANAESTHETICS, LOCAL; ropivacaine, bupivacaine; ANALGESIA, EPIDURAL; ANALGESIA, PATIENT-CONTROLLED; NARCOTICS, sufentanil; OBSTETRICS; PREGNANCY