Epidural analgesia with 0.15% ropivacaine plus sufentanil 0.5 µg ml–1 versus 0.10% bupivacaine plus sufentanil 0.5 µg ml–1: a double-blind comparison during labour

H. J. Clément*,1, L. Caruso1, F. Lopez1, F. Broisin1, M. Blanc-Jouvan1, E. Derré-Brunet1, A. Thomasson1, G. Leboucher2 and J. P. Viale1

1Department of Anaesthesiology, Hôpital de la Croix-Rousse, F-69004 Lyon, France. 2Department of Pharmacy, Hôpital de la Croix-Rousse, F-69004 Lyon, France*Corresponding author

Accepted for publication: January 29, 2002


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. Ropivacaine has been claimed to produce less motor block than bupivacaine during epidural analgesia. However, this advantage has not been clearly confirmed in obstetric studies using low analgesic concentrations in a ratio close to that suggested to be equianalgesic.

Methods. This double-blind, randomized, prospective study was performed in 140 parturients who requested epidural analgesia. After a lumbar epidural catheter had been placed, patients received either 0.10% bupivacaine plus sufentanil 0.5 µg ml–1 or 0.15% ropivacaine plus sufentanil 0.5 µg ml–1 followed by a continuous infusion. Additional boluses were used for inadequate levels of analgesia. Visual analogue pain scores, motor block, level of sensory block, supplementary boluses and main characteristics of labour were recorded.

Results. No differences were observed between the two groups for pain scores, total volume of anaesthetic solution used [59 (23) and 57 (24) ml in the bupivacaine and ropivacaine groups respectively], duration of labour, mode of delivery, side-effects or satisfaction score. The incidence of motor block was not statistically different between the groups (54 and 69% in the bupivacaine and ropivacaine groups respectively, P=0.07). However, when motor block occurred, survival analysis showed that it occurred sooner in the course of labour with ropivacaine compared with bupivacaine (log rank test, P=0.012).

Conclusion. Combined with sufentanil 0.5 µg ml–1, 0.10% bupivacaine and 0.15% ropivacaine produce effective and equivalent analgesia during labour, with similar incidences of motor block.

Br J Anaesth 2002; 88: 809–13

Keywords: anaesthesia, obstetric; anaesthetic techniques, epidural; anaesthetics local, bupivacaine; anaesthetics local, ropivacaine; analgesics opioid, sufentanil


    Introduction
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Epidural anaesthesia is an effective means of providing analgesia during labour. However, its potential for motor block may decrease maternal mobility and satisfaction and may increase the incidence of instrument-assisted deliveries.

Dilute solutions of epidural bupivacaine combined with opioids have been used to minimize the unwanted local anaesthetic effect of motor block. Recently, a new amide local anaesthetic, ropivacaine, was introduced for epidural analgesia during labour, and some studies have suggested that ropivacaine produces less motor block than bupivacaine.1 2 These studies were conducted with similar concentrations of ropivacaine and bupivacaine.

However, two recent studies have shown that, with regard to analgesic effect, ropivacaine is 60% as potent as bupivacaine when used for epidural pain relief in labour.3 4 Therefore, previous comparisons of the incidence of motor block between these two anaesthetics were carried out using relatively more bupivacaine than ropivacaine when the potency difference is considered. This casts some doubt on the validity of the potential benefits of ropivacaine regarding motor block.

The aim of this study was to compare motor block provided by equianalgesic concentrations of ropivacaine (0.15%) and bupivacaine (0.10%) combined with sufentanil 0.5 µg ml–1 for analgesia during labour.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This research was conducted at the Croix-Rousse Hospital, Hospices Civils de Lyon, France. The protocol was approved by the local ethics committee and written informed consent was obtained from each patient. One hundred and forty parturients classified as ASA physical status I or II who requested epidural analgesia were enrolled in the study. An uncomplicated course of pregnancy and normal fetal heart rate before randomization were necessary inclusion criteria. Participants were para 0 or 1, 18–40 yr old, with singleton pregnancy of more than 37 weeks and vertex presentation. All women were in active labour with cervical dilatation of 3–7 cm and a visual analogue pain score (VAPS) greater than 30 mm. None was receiving parenteral opioids before epidural placement.

Patients were placed in the flexed sitting position and were monitored with a non-invasive blood pressure cuff, pulse oximetry and cardiotocography. The epidural space was identified using the saline loss of resistance technique at the L2–L3 or L3–L4 level, and a multiport epidural catheter was advanced 3 cm into the epidural space. Afterwards, a test dose was performed using 1% lidocaine 3 ml.

Participants were allocated to one of two groups in a double-blind, randomized, prospective study design. Patients were assigned to one of the two treatments using a random number table. The procedure of randomization and the handling of the treatment vials was the responsibility of the pharmacy in our institution. Epidural solutions were prepared by the hospital pharmacist, with either 0.10% bupivacaine plus sufentanil 0.5 µg ml–1 or 0.15% ropivacaine plus sufentanil 0.5 µg ml–1. The anaesthetists performing the procedure and subsequent assessment were blinded to the local anaesthetic used. Patients lay on their left side before injection of drugs. According to the patient’s height, the initial bolus was 10 ml (height less than 160 cm), 15 ml (height 160–170 cm) or 20 ml (height greater than 170 cm) and was followed by an infusion of 6–10 ml h–1 according to the patient’s height (greater than 170 cm, 10 ml h–1; less than 160 cm, 6 ml h–1; between 160 and 170 cm, 8 ml h–1).

Pain was assessed with a 100-mm linear visual analogue pain scale (VAPS), on which 0 represented no pain and 100 the worst possible pain. Evaluation was carried out immediately before epidural injection and at 5-min intervals for the first 30 min after bolus injection, then every hour until birth. An additional VAPS score was obtained at the time of delivery. When the patient requested additional analgesia, 5 ml of the study solution was given through the epidural catheter.

In addition to VAPS assessment, other data collected at the same time included maternal blood pressure and heart rate. When blood pressure decreased by more than 20% of the initial value, the patients received a bolus of ephedrine 3–9 mg. Sensory level was determined by a perceived temperature difference to ice at 30 min and every hour until the time of delivery.

Motor block was assessed using a modified Bromage scale (1=complete motor block; 2=able to move the feet; 3=able to move the knees; 4=detectable weakness of hip flexion; able to raise the legs but unable to keep them raised; 5=no detectable weakness of hip flexion). We did not assess for score 6 (able to perform knee-bend while standing) because it was difficult to stand the patients up with our monitoring and because the practice in our hospital is not to allow patients to stand during labour. For statistical analysis, motor block was defined as a modified Bromage scale equal to or lower than 4.

During epidural analgesia, we measured, with a 100-mm linear visual analogue scale (VAS), the side-effects (pruritus, nausea) and, after delivery, the satisfaction of the patients. Finally, we noted the time from epidural administration until delivery, total volume of epidural solution used, mode of delivery and Apgar scores at 1, 5 and 10 min.

Statistical analysis
Data are presented as mean (SD). Patient characteristics and obstetric data were analysed using unpaired Student’s t-test for the parametric variables, Fisher’s exact test for counts and proportions, and the Mann–Whitney U-test for non-parametric data, such as satisfaction and Apgar scores. In order to take into account the unbalanced design (resulting from unequal times to delivery), the effect of treatment on data varying with time (circulatory variables and VAPS) was studied by two-way analysis of variance using a multiple linear regression model with appropriately coded dummy variables. In addition to the analysis of the proportion of motor block in the two groups of patients, the percentages of patients in each group with no motor block were compared over time using Kaplan–Meier survival curves followed by a log-rank test. A P value <0.05 was considered to be significant.

Statistical analyses were performed using SPSS for Windows V9.0 (SPSS, Chicago, IL, USA). Sample size was estimated before the study using the incidence of motor block as primary outcome. On the basis of previous work on the incidence of motor block and an expected reduction of 30% in this incidence, we estimated that a sample size of 70 patients per group was necessary to give the study a power of 0.80 with a type 1 error of 0.05.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
One hundred and forty patients were enrolled in the study. Five patients (three in the bupivacaine group and two in the ropivacaine group) were excluded from data analysis: three patients experienced a failure of analgesia and the epidural catheter had to be replaced, data collection was incomplete in one patient and one patient was delivered before 30 min.

There were no significant obstetric and patient differences between the two groups (Table 1). The duration of labour after epidural injection, the highest thoracic analgesic level and the mode of delivery were similar (Table 2). For both groups, additional boluses were used. Although significantly different among the two groups, the amounts of additional analgesic solution used were small compared with the amount infused [6.4 (0.7) ml in the bupivacaine group compared with 3.5 (0.6) ml in the ropivacaine group]. Therefore, the total volumes of anaesthetic solution used were similar (Table 2). Neonatal Apgar scores were also similar.


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Table 1 Patient characteristics. Data are mean (SD or range). No significant differences between the groups
 

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Table 2 Labour and delivery data. Data are mean (SD) for time to delivery and amount of anaesthetic solution used, median and interquartile range for the highest thoracic level of analgesia, and number of cases for the mode of delivery. None of the variables differed significantly between groups
 
Satisfactory analgesia (VAPS <20 mm) occurred after a mean delay of 11.7 (7.5) min in the bupivacaine group and 12.8 (6.8) min in the ropivacaine group (not significant), and no difference was noted between the two groups during all of labour (Fig. 1). At the time of delivery, mean VAPS score was 17.6 (24.1) mm in the bupivacaine group and 16.7 (26.6) mm in the ropivacaine group (not significant).



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Fig 1 Median visual analogue pain score (VAPS) as a function of time during labour for the two groups of parturients receiving bupivacaine or ropivacaine. The figure shows the median and the upper and lower quartiles.

 
The incidence of motor block was not significantly different between the groups (54 and 69% for bupivacaine and ropivacaine respectively; P=0.07). The distribution of the severity of motor block was also similar (Fig. 2). However, a difference appeared when the time of occurrence was subjected to survival analysis. The probability of being without any block during the course of labour was significantly greater with bupivacaine than with ropivacaine (log rank test, P=0.012) (Fig. 3). Just before delivery, only 10 patients experienced a motor block equal to or lower than 3 on the Bromage scale in the ropivacaine group, compared with six patients in the bupivacaine group (not significant).



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Fig 2 Number of patients at each stage of the Bromage motor block scale in the bupivacaine group and the ropivacaine group.

 


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Fig 3 Proportion of parturients in each group without motor block as a function of time. The bupivacaine group was significantly different from the ropivacaine group. Log rank test, P=0.018.

 
Pruritus was present in 45% of the patients in the bupivacaine group and in 47% in the ropivacaine group, with a mean intensity of 29.7 (21.9) and 36.7 (14.2) mm respectively (not significant). Nausea was present in 17% of the patients in the bupivacaine group and in 25% in the ropivacaine group, with a mean intensity (VAS) of 34.5 (26.7) and 47.7 (32.0) mm respectively (not significant).

The time course of systolic arterial pressure and heart rate during epidural analgesia was similar for bupivacaine and ropivacaine. Six patients in the bupivacaine group (10%) and 10 in the ropivacaine group (15%) received one or more boluses of ephedrine to reverse moderate decreases in maternal arterial blood pressure. None of these episodes was associated with a large decrease (more than 30%) in blood pressure or with an abnormal fetal heart rate pattern.

When all parturients of both groups were considered, satisfaction with the analgesia provided during labour was significantly greater when no motor block was observed [mean VAS of satisfaction, 96.1 (0.9) mm vs 90.0 (1.7) when motor block was present; P=0.02]. There was no difference between study groups in satisfaction score [92.8 (11.9) mm in the bupivacaine group and 91.9 (16.8) mm in the ropivacaine group].


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
We showed that 0.15% ropivacaine with sufentanil 0.5 µg ml–1, when given as a continuous epidural infusion during labour, was as effective as 0.10% bupivacaine with sufentanil 0.5 µg ml–1 and side-effects were similar. Contrary to some previous non-obstetric studies,5 the incidence of motor block was not different between the ropivacaine and the bupivacaine groups, although survival analysis revealed a higher probability to no block during the course of the labour with bupivacaine.

Experimental studies suggest that ropivacaine, contrary to bupivacaine, is more selective for nerve fibres responsible for transmission of pain than for those that control motor function.6 7 Thus, less intense motor block was expected with its clinical use when compared with bupivacaine. Several works have compared the motor block produced by ropivacaine and bupivacaine in obstetrics. Some of them found no difference when comparing high concentrations (0.5 and 0.25%) of local anaesthetics.1 810 When comparing low concentrations of local anaesthetics (0.125, 0.10 and 0.08%), studies showed no difference1113 or less motor block with ropivacaine.5 14 Whatever the concentrations used in these studies, both local anaesthetics were injected epidurally at the same concentration. The results of these previous studies can be questioned as ropivacaine has been suggested to be 40–50% less potent than bupivacaine when the analgesic effect is considered.3 4 Therefore, we used bupivacaine and ropivacaine concentrations in a ratio of 0.67.

Two limitations should be noted regarding the true equipotency of the concentrations chosen. First, the relative potencies of bupivacaine and ropivacaine were estimated with an up–down design in which all data points were concentrated around the 50% effective dose. Therefore, the potency ratio of 0.6 found in these studies is only valid for the median effective analgesic concentration and does not permit conclusions about the potency ratio of higher doses. The second limitation is secondary to the simultaneous use of an opioid. This causes a marked reduction in the minimum local analgesic concentration, implying that the analgesic effect of the mixture we used was located on the upper part of the dose–response curve. In fact, a very recent study reported satisfactory analgesia during labour with 0.07% ropivacaine.15 Thus, high concentrations could have hidden any difference between the two anaesthetics. Indeed, the concentrations we used were very close to that described by Capogna and colleagues,4 who investigated the minimum local analgesic concentrations of epidural bupivacaine and ropivacaine without the addition of opioids (0.093% and 0.156% respectively). Any imbalance in the equianalgesic concentrations used in the present study could have explained the slight difference in motor block. Interestingly, since we completed our work, another study16 has been published comparing the two anaesthetics combined with fentanyl in concentrations in the same ratio (0.6) but at lower values, very close to those found by Polley and colleagues for the 50% effective dose (0.0625% and 0.1%). Although they observed less motor block for both anaesthetics owing to the lower concentration used, no difference in the recorded pain intensity or degree of motor block was observed

In summary, we found that epidurally administered 0.10% bupivacaine and 0.15% ropivacaine combined with sufentanil 0.5 µg ml–1 produced equivalent and adequate sensory block for patients in labour and were well tolerated. Although the occurrence of motor block was similar for the two anaesthetics, block occurred sooner when ropivacaine was administered.


    Acknowledgements
 
The authors thank Dr François Chapuis and Dr Muriel Rabilloud of the Department of Medical Information for assistance in the statistical analysis of the data. The authors also thank the anaesthetics nursing staff (IADE) for their invaluable support and Mrs A. Desmazes and A. Dumont for secretarial help.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Eddleston JM, Holland JJ, Griffin RP, et al. A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia in labour. Br J Anaesth 1996; 76: 66–71[Abstract/Free Full Text]

2 Zaric D, Nydahl PA, Philipson L, et al. The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and motor block in volunteers: a double-blind study. Reg Anesth 1996; 21: 14–25[ISI][Medline]

3 Polley LS, Columb MO, Naughton NN, Wagner DS, van de Ven CJ. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology 1999; 90: 944–50[ISI][Medline]

4 Capogna G, Celleno D, Fusco P, Lyons G, Columb M. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999; 82: 371–3[Abstract/Free Full Text]

5 Gautier P, De Kock M, Van Steenberge A, et al. A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125% bupivacaine with sufentanil for epidural labor analgesia. Anesthesiology 1999; 90: 772–8.[ISI][Medline]

6 Bader AM, Datta S, Flanagan H, Covino BG. Comparison of bupivacaine- and ropivacaine-induced conduction blockade in the isolated rabbit vagus nerve. Anesth Analg 1989; 68: 724–7[Abstract]

7 Wildsmith JA, Brown DT, Paul D, Johnson S. Structure–activity relationships in differential nerve block at high and low frequency stimulation. Br J Anaesth 1989; 63: 444–52[Abstract]

8 McCrae AF, Jozwiak H, McClure JH. Comparison of ropivacaine and bupivacaine in extradural analgesia for the relief of pain in labour. Br J Anaesth 1995; 74: 261–5.[Abstract/Free Full Text]

9 Stienstra R, Jonker TA, Bourdrez P, et al. Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: a double-blind comparison. Anesth Analg 1995; 80: 285–9[Abstract]

10 Gaiser RR, Venkateswaren P, Cheek TG, et al. Comparison of 0.25% ropivacaine and bupivacaine for epidural analgesia for labor and vaginal delivery. J Clin Anesth 1997; 9: 564–8[ISI][Medline]

11 Fischer C, Blanie P, Jaouen E, et al. Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison. Anesthesiology 2000; 92: 1588–93[ISI][Medline]

12 Owen MD, D’Angelo R, Gerancher JC, et al. 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient-controlled epidural infusion. Anesth Analg 1998; 86: 527–31[Abstract]

13 Campbell DC, Zwack RM, Crone LA, Yip RW. Ambulatory labor epidural analgesia: bupivacaine versus ropivacaine. Anesth Analg 2000; 90: 1384–9[Abstract/Free Full Text]

14 Meister GC, D’Angelo R, Owen M, Nelson KE, Gaver R. A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor. Anesth Analg 2000; 90: 632–7[Abstract/Free Full Text]

15 Vallejo M, Firestone L, Mandell G, et al. Effect of epidural analgesia with ambulation on labor duration. Anesthesiology 2001; 95: 857–61[ISI][Medline]

16 Fernandez-Guisasola J, Serrano ML, Cobo B, et al. A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl for continuous epidural labor analgesia. Anesth Analg 2001; 92: 1261–5[Abstract/Free Full Text]