Epidural block is an effective means of providing analgesia in labour. Bupivacaine is the most commonly used local anaesthetic during labour, but limitations to its usefulness include motor block and cardiovascular toxicity. Recent attempts have been made to reduce bupivacaine-induced side-effects and toxicity [1,2]. Ropivacaine, the S-enantiomer of N-propylpipecolic acid 2,6-xylidine, was developed to address some of these issues. Ropivacaine is a long-acting amide local anaesthetic agent available for epidural analgesia during labour . It has lower cardiotoxicity compared with bupivacaine . Ropivacaine may also be more selective for sensory fibres compared with other local anaesthetics, producing less motor block [5,6]. These properties suggest that ropivacaine could be superior to bupivacaine in obstetric analgesia. Recent clinical studies comparing ropivacaine 0.125-0.25% with bupivacaine at equal concentrations reported not only comparable analgesia, but also comparable motor blockade [4,7-9].
In the present study, the efficacy of bupivacaine/fentanyl and ropivacaine/fentanyl in providing labour and delivery analgesia was evaluated. Fentanyl was chosen rather than other opioids because of its high lipid solubility and high affinity for the μ-opioid receptor. Fentanyl was added to the ropivacaine or bupivacaine as it reduces the local anaesthetic requirement by approximately 25% . The purpose of the present study was to evaluate the effects of bupivacaine 0.2% compared with ropivacaine 0.2% combined with fentanyl for analgesia during labour and to detect the subtle differences in motor block by decreasing the cumulative local anaesthetic dose.
The institutional review board of the University of Ankara Faculty of Medicine, Turkey, approved the study. Informed consent was obtained from 60 nulliparous women (ASA I-II) who required epidural analgesia. They had uncomplicated pregnancies with a single fetus in a vertex presentation. All parturients were at term and none had any significant coexisting disease. None received any analgesic agent before participation in the study. Exclusion criteria included weight >115 kg, inability to cooperate, allergy to local anaesthetics and opioids, women with spinal column disorders, and women who had undergone spinal surgery.
Patients were placed in the lateral position and after fluid loading with 500 mL lactated Ringer's solution, a multiorifice epidural catheter (B. Braun Medical, Melsungen, Germany) was inserted 3-4 cm into the epidural space at the L2-3 or L3-4 lumbar level by a hanging drop technique. Intravascular placement was excluded by active aspiration of the catheter and by inspection of a dependent catheter for passive blood reflux. In the case of evident or questionable blood reflux, the catheter was removed and reinserted at a higher epidural space. Lidocaine 3 mL 2% was administered as a test dose to rule out intrathecal application.
Parturients were randomly allocated into two groups using a computer-generated table of random numbers and the initial doses were given epidurally during the active phase of labour when the cervical dilatations were between 3-7 cm. By double-blinded design, the first group received bupivacaine 0.2% (Marcaine®; Eczacıbaşı, Turkey) with fentanyl 2 μg mL−1 (B/F) (n = 30), and second group received ropivacaine 0.2% (Naropin®; Astra, Sweden) with fentanyl 2 μg mL−1 (R/F) (n = 30). The study solutions were prepared by an anaesthesiologist not directly involved in the patient's care or data collection. Parturients and physicians were also blinded to the study solutions administered. For the initiation of epidural analgesia, 8 mL of the study solution was administered. Parturients not experiencing analgesia within 15 min of administration of the study drug were excluded. Supplemental analgesia was obtained with 4 mL of the study solution according to parturients' needs (Visual Analogue Scale (VAS) ≥ 4) throughout labour. Top-up doses were repeated at least every 20 min throughout labour. Patients who experienced inadequate analgesia during labour who required manipulation of the epidural catheter, or who delivered within 2 h of the epidural catheter placement were excluded from data analysis.
The onset of analgesia was assessed using a pain relief score (0, no relief; 1, poor relief; 2, significant relief; 3, complete relief) evaluated by the parturient during the first contractions after the epidural injection. A score of 2-3 was considered satisfactory. The onset of analgesia was taken as the elapsed time between the initial epidural injection of the study drug and satisfactory analgesia being obtained. Pain was assessed with a 10 cm linear VAS immediately before the injection of the loading dose and every 5 min for 30 min, and then every 20 min after epidural injection until delivery. Patients were asked to rate pain intensity during uterine contractions. The two methods of pain assessment were used concurrently. The duration of the analgesia provided by the epidural solutions was taken as the elapsed time between the initial epidural injection and the subsequent additional analgesic request. Additionally, duration of labour and hourly local anaesthetic doses were recorded. No analgesic agents other than the study solutions were given. The overall quality of analgesia was judged by both patients and investigators after delivery as excellent, good, fair, poor or absent.
Motor block of the lower limbs was assessed using a modified Bromage scale: 0, no motor block (none); 1, inability to raise the extended leg, able to move knees and feet (mild); 2, inability to raise the extended leg or move kness, able to move feet (moderate); and 3, complete motor block of the limbs (severe). Motor block was assessed every 5 min for 30 min and then every 20 min after epidural injection until delivery. Sensory block was assessed using bilateral pinprick tests in the mid-clavicular line. Thirty minutes after each epidural injection, patients subjectively rated nausea, sed-ation and pruritus using VAS. These parameters were also recorded after each 30 min.
Maternal and fetal cardiovascular variables were measured every 5 min for 30 min after the loading dose and subsequently at 20 min intervals until the end of labour. A respiratory rate <10 breaths min−1 was noted as respiratory depression. Oxyhaemoglobin saturation was monitored continuously by pulse oximetry in all patients. Baseline values for blood pressure and heart rate were the mean of the three measurements performed before epidural injection. After the initiation of epidural analgesia, mild hypotension was defined as systolic blood pressure between 90 and 100 mmHg, moderate hypotension as a systolic blood pressure between 80 and 90 mmHg and severe hypotension as a systolic blood pressure <80 mmHg. Fetal heart rate and uterine activity were monitored continuously throughout labour.
The mode of delivery was recorded as spontaneous, forceps assisted or by Caesarean section. In the second stage of labour, perineal analgesia was sometimes inadequate (VAS > 4) despite supplemental bolus doses. If additional perineal anaesthesia was needed for delivery, patients received lidocaine 2% 10-15 mL. A neonatalogist evaluated the babies by Apgar scoring at 1, 5 and 10 min after birth. The study was terminated at the time of vaginal delivery.
Statistical analysis included Wilcoxon signed rank sum rest, χ2, Fisher's exact and t-tests, as appropriate. P < 0.05 was considered as significant. Results are expressed as mean ± SD unless otherwise stated. Group size (28 patients in B/F, 25 patients in R/F) was selected by using proportions sample size estimates (power = 80%, α = 0.05) to detect a 35% difference in the occurrence of motor block between groups. The incidence of significant motor block (2 or 3 on a 0-3 scale) was assumed to be 25%.
Sixty patients were enrolled and 53 completed the study: 28 received bupivacaine-fentanyl and 25 ropivacaine-fentanyl. There were no significant demographic differences between groups in respect to age, weight, height, gestational age, effacement and cervical dilatation (Table 1). Sixty patients were enrolled in the protocol; however, seven patients were eliminated for the following reasons: accidental catheter removal (one in the ropivacaine group), incomplete data collection (one in the bupivacaine, two in the ropivacaine group) and Caesarean section decisions in three parturients (two in the ropivacaine, one in the bupivacaine groups).
Analgesia and epidural characteristics
The median onset time for pain relief after the loading dose was similar in the R/F (11.2 ± 3.13 min) and B/F (10.5 ± 4.43 min) groups (Table 2). The duration of analgesia after the loading dose in B/F group lasted slightly longer than in the R/F group (98.6 ± 21.2 versus 84.5 ± 13.7 min), but there was no statistical significance (Table 2). Adequate analgesia was obtained with both drugs as VAS remained stable and was similar in both groups throughout the study. The hourly local anaesthetic use was similar in both groups (Table 2). The hourly dose of ropivacaine was 10.1 ± 2.6 mL. For bupivacaine, the hourly dose was 11.2 ± 3.1 mL. The mean total volume of ropivacaine/fentanyl administered from epidural catheter placement until delivery was 58.5 ± 18.2 mL (ropivacaine 117.0 ± 36.4 mg, fentanyl 117.0 ± 36.4 μg) versus 71.2 ± 21.3 mL (142.4 ± 42.6 mg bupivacaine, 142.4 ± 42.6 μg fentanyl) bupivacaine/fentanyl and did not differ between groups. Each mean total dose included the initial 8 mL epidural bolus and supplemental boluses of the study solution administered during labour, but it does not include the lidocaine boluses administered immediately before delivery. None of the patients completing the study had poor analgesia.
A similar median level of sensory loss to pinprick in the mid-clavicular line was observed in all patients in the different study groups (T8-9). The overall quality of analgesia as judged by parturients and investigator was satisfactory in both groups.
Labor and delivery characteristics
The duration of labour and use of oxytocin did not differ between groups. Of the 25 patients in the R/F group, 15 received oxytocin compared with 16 of 28 patients in the B/F group. The incidence of instrumental delivery was higher in the B/F group than the R/F group (15 versus 7, respectively) (P < 0.05). We did not attempt to control for instrumental deliveries. Additional perineal anaesthesia was needed for delivery in eight patients in the R/F group, cf. only two patients in the B/F group (8 versus 2, respectively, P < 0.05). The indication for Caesarean section was cephalopelvic disproportion (two in the R/F group, one in the B/F group) (Table 3). Apgar scores were similar between groups.
Mild hypotension was the predominant local anaesthetic side-effect observed in the study in both groups. Systolic blood pressure did not fall below 90 mmHg in any patient. No patient required the administration of supplemental fluid loading or ephedrine. None of these episodes were associated with an abnormal fetal heart rate pattern (Table 2).
Motor block was observed in 13 patients in the B/F group (45%) whereas two patient had motor block in the R/F group (8%) (P < 0.05). Of these 13 patients in the B/F group, three (10%) developed moderate block (2 on a 0-3 scale). Ten patients in the B/F group and two in the R/F group developed mild block (1 on a 0-3 scale) (Fig. 1). Motor block was observed 216 ± 32 min after the initial dose of epidural ropivacaine/fentanyl, cf. 195 ± 38 min in the bupivacaine/fentanyl group. The average duration of the motor block was 85 ± 37 min in the B/F group and 40 ± 24 min in the R/F group (P < 0.05).
Pruritus occurred in three patients (two in the R/F, one in the B/F group), but did not require treatment. Shivering was not reported in any group. Urinary retention was observed in one patient in the B/F group; however, urinary catheterization was not required. Pain relief was associated with light sedation in 30% of all parturients.
Three patients in the B/F group and two patients in the R/F group presented with nausea. Respiratory rates did not fall below 10 breaths min−1 in any patient. Oxyhaemoglobin saturation was >95% in all patients at all times. The subsequent course of the parturients was uneventful.
The results indicate that epidural ropivacaine 0.2% combined with 2 μg mL−1 fentanyl produced adequate analgesia for the initiation and maintenance of labour pain. The duration of analgesia was comparable with the pain relief afforded by bupivacaine 0.2% combined with fentanyl 2 μg mL−1. Furthermore, ropivacaine 0.2% combined with fentanyl 2 μg mL−1 provided effective analgesia with significantly less motor block and instrumental delivery than bupivacaine/fentanyl combination at the same concentrations during labour. These results are similar to previous studies when either fentanyl or sufentanil was added to all concentrations of ropivacaine <0.20% for the relief of labour pain [3,10]. The cumulative dose of ropivacaine in the present study may have decreased below the threshold for producing motor block, thus allowing us to detect subtle differences in motor block between ropivacaine and bupivacaine.
To date, ropivacaine has been administered in clinical practice by several routes and over a range of concentrations (0.1-1%). Obstetric anaesthesiologists tend to use, for epidural analgesia, the lowest possible concentration of a local anaesthetic that offers adequate pain relief in labour. Using the lowest concentration reduces the resultant motor block, which may decrease the incidence of either instrumental deliveries  or Caesarean sections , although this is controversial . We are not aware of any study that has determined whether concentrations of ropivacaine <0.20% without adjuvants, provide adequate analgesia for the relief of labour pain. However, the lowest effective concentration of ropivacaine without opioid as a standard for epidural analgesia during labour has recently been determined. Beilin and colleagues  recommend that if ropivacaine is selected as the sole local anaesthetic for the initiation of epidural analgesia in labour, the minimal concentration should be 0.2%. Similarly, Cascio and colleagues  found that ropivacaine 0.2% produced adequate analgesia for the initiation and maintenance of epidural analgesia in labour. For these reasons, we chose to administer a 0.2% concentration of ropivacaine and bupivacaine, and added fentanyl to compare the effects of two combinations. However, Gautier and colleagues  and Meister and colleagues  used 0.125% concentrations of ropivacaine and bupivacaine and added an opioid (sufentanil, fentanyl respectively) and they compared the effects of these combinations. Gautier and colleagues  used the ropivacaine 0.125% and sufentanil combination for the initiation of analgesia and found that this combination affords reliable analgesia with minimal motor block. This study cannot be compared with ours because we studied ropivacaine for the initiation and maintenance of epidural analgesia. Meister and colleagues  reported that ropivacaine 0.125% plus fentanyl 2 μg mL−1 and bupivacaine 0.125% plus fentanyl 2 μg mL−1 produced equivalent analgesia with less motor block in the ropivacaine group. However, several factors differ from the present study. First, we studied only nulliparous women, whereas 48% of parturients were nulliparous in Meister and colleagues' study. Pain scores seem to be higher in nulliparous than multiparous women. Second, although Meister and colleagues used a lower concentration of ropivacaine, the total dose of ropivacaine (113 mg) they used is similar to ours (117 mg). Therefore, the low concentration of ropivacaine (0.125%) may have no advantage over the 0.2% concentration except that a lower concentration of local anaesthetic may be safer in case of accidental intravenous injection.
Although we tried to control factors carefully such as age, parity and physical status of the subjects, we did not take into consideration factors such as socio-economic status, intra- or intercultural variation among the groups that may affect our results. Cultural backgrounds, however, have a powerful effect on the pain perception threshold and pain tolerance levels. For example, levels of radiant heat that are reported as painful by people of Mediterranean origin are described merely as warmth by North Europeans . This may partly explain the discrepancies between studies at which a higher concentration of local anaesthetic is needed for pain relief during labour in certain countries whereas a lower concentration of local anaesthetic is adequate in others.
Fentanyl appeared to be ideal for pain relief in labour because it selectively affects pain perception while sparing the autonomic and motor pathways . Several investigators reported that epidural fentanyl reduced local anaesthetic requirements by 19-31% [18,19]. Although we could not demonstrate the ability of fentanyl to reduce the cumulative dose in the current study, the average dosage of local anaesthetic used seems to be lower compared with the other studies in which the local anaesthetic was the sole agent [7,8,20]. The low local anaesthetic dose used in the present study represents a negligible risk in the event of accidental intravascular or intrathecal administration.
Although it has been proposed that the separation of sensory from motor block with ropivacaine may be clinically apparent only at lower concentrations, epidural studies in labour using ropivacaine or bupivacaine 0.125-0.25% have shown some difference in the magnitude of motor block [3,7]. Eddlestone and colleagues  compared epidural ropivacaine 0.25% and bupivacaine 0.25% for the relief of labour pain and reported that the incidence, intensity and duration of motor block were slightly less in the ropivacaine group. They also stated that the ropivacaine group had a higher incidence of spontaneous vaginal delivery (70.59 versus 52.00%). Likewise, we found less motor block in patients receiving ropivacaine 0.2% combined with fentanyl in the present study. The intensity and duration of motor block were less in the R/F group. Similarly and possibly linked was the finding that a lower number of women in this group required instrumental delivery (28 versus 53%). Although not statistically significant, the higher total amount of local anaesthetic used in B/F group is likely to inhibit the bearing down reflex as a consequence of motor blockade. Unfortunately, one criticism of the modified Bromage score is that it estimates the degree of motor blockade in the muscles of the lower limbs and not in the muscles involved in the birth process. It would have been possible to detect any differences in motor blockade in the muscles involved in the delivery accurately if a more sensitive assessment of motor function of abdominal wall had been used. These issues are probably contributing factors in the higher incidence of instrumental delivery in the B/F group.
Possible reasons for the lesser motor block in the ropivacaine group may be due to several factors. First, the reduction of motor block may be related to the lower potency of ropivacaine compared with bupivacaine: three recent studies suggest that ropivacaine is 40-50% less potent than bupivacaine [21-23]. However, parturients administered bupivacaine/fentanyl required significantly more supplemental analgesia during labour than parturients given ropivacaine/fentanyl in the present study. The opposite would be predicted if ropivacaine were significantly less potent than bupivacaine. On the other hand, the fact that bupivacaine/fentanyl had a slightly faster onset and longer duration than ropivacaine/fentanyl suggests that bupivacaine might be more potent than ropivacaine in the current study. The finding supports the evidence that ropivacaine is less potent than bupivacaine . Therefore, from the results obtained in the current study, we could not determine that a lesser motor blocking effect of ropivacaine was directly related to its lower potency. To find the answer to this question, comparison trials need to be completed with full knowledge of the relative potencies or the respective dose-response curves for bupivacaine and ropivacaine. We believe that further discussion of the relative potencies of ropivacaine and bupivacaine is warranted. Second, concerning the bupivacaine-induced motor block, Russell and Reynolds  demonstrated that motor block is dependent on the cumulative dose of local anaesthetic agent. In other words, motor block becomes progressively more severe with the duration of epidural analgesia. As the cumulative dosage of bupivacaine administered in the present study was higher (not statistically significant) compared with ropivacaine, motor block became more severe with the duration of epidural analgesia. Third, the differences in motor block observed in this study may be related to the physiochemical properties of the two drugs. Fourth, the motor block scoring system used in this study, however, was not highly sensitive and may not have uncovered slight differences between groups, if they existed. A more sensitive and quantitative test is isometric abdominal wall assessment . This procedure, however, is more difficult to use and unfamiliar to most anaesthesia providers. We selected the current method because it was simple and clinically useful in detecting gross differences in motor block. Differences less than those observed by this scoring system may be clinically irrelevant.
Pruritus is a recognized side-effect after epidural fentanyl, but this symptom was elicited only on direct questioning . Three patients in the present study thought itching was only mild and required no treatment.
At the time of delivery, more patients in the R/F group required additional perineal anaesthesia for episiotomy simply because they had received less additional supplementation (although not significant, the total dosage of local anaesthetic was lower) in this group. One possible explanation is that ropivacaine analgesia may not be dense enough to produce adequate analgesia at delivery. This finding also supports the evidence that ropivacaine is less potent than bupivacaine . However, similarity in VAS throughout labour and immediately after delivery, as well as overall mother satisfaction between groups, also suggests both solutions produce equivalent analgesia.
Assessment of the effect of a local anaesthetic on the fetus is always difficult and relies largely on evaluation of the infant at delivery and over the ensuing hours. However, there were no significant fetal heart rate abnormalities noted throughout labour in any patient. Traditionally, neonatal condition has been assessed by the Apgar scoring system.
In conclusion, epidural bupivacaine 0.2% and ropivacaine 0.2% each combined with 2 μg mL−1 fentanyl produced adequate and equivalent analgesia for pain relief during labour and delivery. It is concluded that ropivacaine 0.2% combined with fentanyl 2 μg mL−1 provided effective analgesia with significantly less motor block and instrumental delivery than bupivacaine/fentanyl combination at same concentrations during labour and delivery.
No commercial funding was received for this study.
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