Minimum local analgesic concentrations of ropivacaine and levobupivacaine with sufentanil for epidural analgesia in labour

doi:10.1016/j.ijoa.2009.02.002

International Journal of Obstetric Anesthesia

Volume 18, Issue 3, July 2009, Pages 226-230

https://doi.org/10.1016/j.ijoa.2009.02.002 Get rights and content

Abstract

Background

Sufentanil is often added to ropivacaine and levobupivacaine to provide epidural analgesia in labour. The aim of this study was to compare the analgesic potencies of epidural ropivacaine and levobupivacaine in combination with sufentanil 0.5 μg/mL, using the minimum local analgesic concentration (MLAC) model with up-down sequential allocation.

Methods

In this prospective study parturients with cervical dilation ⩾ 3 cm who requested epidural analgesia between 0800 and 1500 were enrolled. They were randomly allocated to receive 20 mL of either ropivacaine (group R) or levobupivacaine (group L) both with sufentanil 0.5 μg/mL. Thirty minutes after initial injection a continuous infusion was started and maintained until delivery. The numbers of additional doses of 0.2% ropivacaine and 0.25% levobupivacaine needed to maintain the visual analogue pain score <10/100 mm were recorded. The median effective concentrations were estimated from up-down sequential allocations and overall dose requirements of ropivacaine and levobupivacaine were compared.

Results

53 women were recruited to the study. The MLAC of ropivacaine was 0.023% w/vol (95% CI, 0.005-0.041) compared with levobupivacaine which was 0.020% w/vol (95% CI, 0.008-0.032). The hourly dose of ropivacaine was 13.3 (SD 5.8) mg/h which was similar to levobupivacaine 14.4 (SD 9.7) mg/h. The total doses used for labour analgesia were 56.1 (SD 32.3) mg of ropivacaine (n = 26) and 58.6 (SD 27.5) mg of levobupivacaine (n = 26).

Conclusion

When sufentanil 0.5 μg/mL was added to either ropivacaine or levobupivacaine for labour analgesia, no significant difference in analgesic potency was observed.

Introduction

Ropivacaine, levobupivacaine and bupivacaine can each provide effective epidural analgesia during labour. The relative analgesic potencies of ropivacaine and levobupivacaine have been extensively evaluated using the MLAC model with up-down sequential allocation.1, 2, 3, 4, 5 Levobupivacaine has been shown to be similar or slightly less potent than bupivacaine, and ropivacaine less potent than bupivacaine.1, 2, 3, 4, 5

Motor blockade is an unwanted side effect during labour analgesia. Several studies have reported less motor blockade with ropivacaine than bupivacaine, and this difference has been attributed to pharmacological differences rather than differences in potency.6, 7, 8 Motor block is more frequent when high concentrations of local anaesthetics are used, so the addition of an opioid allowing a lower concentration to be used is beneficial during labour analgesia.9, 10, 11

In our institution sufentanil 0.5 μg/mL is added to either ropivacaine or levobupivacaine for labour analgesia, as it has been shown to reduce local anaesthetic requirement and minimise motor block.¹² However, the same study demonstrated MLAC values of epidural bupivacaine, ropivacaine and levobupivacaine when given alone that were considerably higher than those previously reported. This may be explained by the lower epidural volume 10 mL compared to previously published studies using 20 mL.1, 2, 3, 4, 5, 13 Consequently we designed a randomized study to compare the MLAC of epidural ropivacaine and levobupivacaine in combination with sufentanil 0.5 μg/mL (10 μg) in parturients requesting relief of labour pain. We used the MLAC model with up-down sequential allocation with a bolus volume of 20 mL.

Section snippets

Methods

The study was conducted at the University Hôpital Maison Blanche of Reims, France, from January to December 2006. After ethical approval by our institutional review board and written informed consent, parturients in spontaneous labour requesting epidural analgesia were enrolled in this randomized study. Women were eligible if they were 18-40 years of age, American Society of Anesthesiologists class I or II, more than 36 weeks of gestation, cephalic presentation, cervical dilation 3-7 cm, and

Statistical analysis

Demographic and obstetric data were collected and presented as mean (SD) or median (range) as appropriate. The median effective concentrations of ropivacaine and levobupivacaine were estimated from the up-down sequential allocation using the Dixon and Massey formula,¹⁵ from which MLAC values with 95% confidence interval (CI) were determined. We chose a sample size identical to those of the previously published studies of MLAC for labour analgesia. In the second part of the study, the mean

Results

We enrolled 53 parturients in the study, 27 in group R and 26 in group L. One parturient was rejected in group R because of failure of epidural analgesia; none were rejected in group L. The groups had similar demographic and obstetric characteristics (Table 1).

The sequences of effective and ineffective analgesia are shown in Fig. 1. The concentrations tested ranged from 0.08 to 0.005%. The MLAC of ropivacaine was 0.023% (95% CI, 0.005-0.041) and for levobupivacaine 0.020% (95% CI, 0.008-0.032),

Discussion

We have demonstrated that when sufentanil 0.5 μg/mL is added to solutions of ropivacaine and levobupivacaine for epidural analgesia in labour, their potencies are similar. This is consistent with the findings of Benhamou et al. and Polley et al. both studies demonstrating that ropivacaine and levobupivacaine are equipotent.1, 5 To compare the potencies of epidural ropivacaine and levobupivacaine, we calculated their median effective concentrations (EC50) using the MLAC model with up-down

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Cited by (30)

Investigation of the Minimum Local Analgesic Concentration of Epidural Sufentanil Combined With Ropivacaine for Labor Analgesia
2020, Clinical Therapeutics
Citation Excerpt :
Our study used the up–down sequential allocation of MLAC analgesia to study the concentration of ropivacaine in analgesia delivery. The up–down sequential allocation is a simple, fast, and approximate method for determining the effective amount, which was first performed by Dixon et al.28–30 In this method, the subjects are tested sequentially one by one. According to the previous reaction, the dose used in the later trials is determined.
Worldwide, there are only few studies focusing on labor analgesia on the MLAC (minimum local analgesic concentration) or EC50 (median effective concentration) of sufentanil and ropivacaine. Therefore, we determine the MLAC or EC50 of sufentanil and ropivacaine for epidural analgesia by using an up–down sequential allocation and survey its adverse effect in a prospective blinded randomized trial.
Sixty nulliparous full-term parturients who required labor analgesia were recruited and randomly divided into the sufentanil and ropivacaine groups. The formulation was 25 μg sufentanil combined with 0.1% ropivacaine (added 0.9% normal saline to 75 ml). According to the response of a previous parturient, the dosage of sufentanil was increased or decreased by 5 μg in the sufetanil group; meanwhile, we also administrated an initial concentration of 0.1% ropivacaine combined with 22.5 μg sufentanil (added 0.9% normal saline to 75 ml) in the ropivacaine group. The concentration of ropivacaine was increased or decreased by 0.01% following the response of the previous parturient. The Brownlee up–down sequential allocation was used to estimate the MLAC of epidural ropivacaine and its 95% confidence intervals in labor analgesia.
There were no significant changes for the two groups, including for age, height weight, active stage, second stage of labor, and gestational weeks (P = 0.769, 0.900, 0.603, 0.441, 0.577, and 0.695, respectively). The VAS scores of the parturient decreased to varying degrees (P < 0.0001) after labor analgesia compared with VAS before labor analgesia, and the most effective analgesia was reached in 60 min. The EC50 dose of epidural ropivacaine combined with 0.3 μg/mL sufentanil was 0.09687%, and the 95% CI was 0.08944%~0.1043%. Five parturients had PONV, and the incidence rate was 16.7%; one parturient had pruritus, so the incidence rate was 3.3%. The EC50 dose of epidural sulfetanil combined with 0.1% ropivacaine was 18.76 μg with a 95% confidence interval of 13.5–24.48 μg. There were no significant differences in the active stage, second stage of labor, and maternal and fetal hemodynamic data between the two groups. Notably, the Apgar scores for 1 min and 5 min were 10 scores for almost all of these patients. There were no significant differences between the two groups for maternal and fetal side effects, which had very low incidence rates.
The MLAC of epidural sufentanil or ropivacaine could provide satisfactory and safe analgesia for parturients while having a low incidence rate of side effects.
Effective concentration of levobupivacaine and ropivacaine in 80% of patients receiving epidural analgesia (EC80) in the first stage of labour: A study using the Continual Reassessment Method
2018, Anaesthesia Critical Care and Pain Medicine
Citation Excerpt :
This large difference in potency might not be clinically relevant in daily practice, if the local anaesthetic is combined with a lipophilic opioid, which exerts a significant and dose-dependent sparing effect on the MLAC values [19,21,23,30]. Because the association with sufentanil may suppress the MLAC differences for levobupivacaine and ropivacaine, it would be of interest to determine if the adjunction of fentanyl or sufentanil also minimises the difference in potency at the level of the EC80 [31]. We a posteriori fitted a logistic equation to the data using non-linear regression and a Bootstrap analysis.
A comparison of the effective dose in 50% of patients (ED50) has suggested that the potency of levobupivacaine lies between that of bupivacaine and ropivacaine. However, for clinical purposes, knowledge and use of doses close to the ED95 are more relevant. This study was designed to determine the EC80 (effective concentration) for both epidural levobupivacaine and ropivacaine using the Continual Reassessment Method (CRM) during obstetric analgesia.
In this double-blind randomised study, term parturients were included by cohorts of 6 if cervical dilatation was ≤ 5 cm and visual analogue pain score (VAPS) > 30 mm. Efficacy was defined by a decrease of VAPS to a value ≤ 10, thirty minutes after epidural injection of 20 mL of levobupivacaine or ropivacaine. The first cohort received the lowest dose. Every next cohort received a dose according to the response's probability calculated using a Bayesian method, incorporating data from all consecutive previous patients. In addition, a logistic equation was fitted a posteriori to the whole data set to determine the whole dose-probability curve.
Fifty-four patients were enrolled. Levobupivacaine 0.17% and ropivacaine 0.2% gave probabilities of success of 82% and 72% respectively. By fitting the logistic model to the data, the concentration leading to a probability of 0.8 (EC80) was 0.14% for levobupivacaine and 0.24% for ropivacaine while the EC50 were 0.09% for levobupivacaine and 0.17% for ropivacaine, respectively.
This study suggests that epidural levobupivacaine used as the sole drug for labour analgesia has an EC80 lower than that of ropivacaine.
Strategies to reduce neuraxial analgesia failure during labour
2016, Trends in Anaesthesia and Critical Care
Citation Excerpt :
Hence, the use of traditional high dose LA epidural infusions is no longer justifiable. The addition of opioids to the epidural infusion provides LA sparing effects [46,47]. A recently published meta-analysis that included 24 randomised controlled trials comparing three commonly used epidural opioids (morphine, fentanyl and sufentanil) showed similar analgesic efficacy and no difference in dose requirements between the fentanyl and sufentanil groups [48].
Labour neuraxial analgesia failure may lead to inadequate pain relief and patient dissatisfaction. This may occur due to difficulty in epidural placement during the initiation of, or during the maintenance of epidural analgesia. In this review, we investigate the risk factors associated with labour neuraxial analgesia failure and present the recent evidence to improve epidural space identification. Demographic and anaesthetic factors that may increase breakthrough pain are discussed. We also examine the effect of different regimens of local anaesthetic agents and analgesic adjuvants on the quality of analgesia. The use of patient controlled epidural analgesia and novel epidural delivery systems such as the role of intermittent epidural automated boluses are explored.
Failed epidural: Causes and management
2012, British Journal of Anaesthesia
Citation Excerpt :
A meta-analysis from 1998 showed that epidural fentanyl was a beneficial adjuvant to local anaesthetics for surgical analgesia, improving pain therapy and with a low incidence of nausea and pruritus.70 The addition of opioids allows for lower concentrations of local anaesthetic, potentially reducing motor block after operation or during labour.71 It has been suggested that the concept of low-dose local anaesthetics for analgesia is feasible only when adjunct opioids are used.72
Failed epidural anaesthesia or analgesia is more frequent than generally recognized. We review the factors known to influence the success rate of epidural anaesthesia. Reasons for an inadequate epidural block include incorrect primary placement, secondary migration of a catheter after correct placement, and suboptimal dosing of local anaesthetic drugs. For catheter placement, the loss of resistance using saline has become the most widely used method. Patient positioning, the use of a midline or paramedian approach, and the method used for catheter fixation can all influence the success rate. When using equipotent doses, the difference in clinical effect between bupivacaine and the newer isoforms levobupivacaine and ropivacaine appears minimal. With continuous infusion, dose is the primary determinant of epidural anaesthesia quality, with volume and concentration playing a lesser role. Addition of adjuvants, especially opioids and epinephrine, may substantially increase the success rate of epidural analgesia. Adjuvant opioids may have a spinal or supraspinal action. The use of patient-controlled epidural analgesia with background infusion appears to be the best method for postoperative analgesia.
Effects of epidural analgesia on uterine artery Doppler in labour
2011, British Journal of Anaesthesia
The effects of epidural anaesthesia on maternal uteroplacental blood flow in the presence of uterine contractions remain unclear. The aim of our study was to evaluate the effects of epidural analgesia with bolus doses on uterine artery pulsatility index (UtA-PI) during labour.
In a prospective case–control study, UtA-PI was measured during uterine contraction and relaxation in nulliparous women in active labour with (epidural group) and without (control group) epidural analgesia. Patients in the two groups were matched for gestational age at delivery, American Society of Anesthesiologists physical status score, and cervical dilatation at the beginning of labour. In the epidural group, an epidural catheter was placed after prehydration with 500 ml i.v. saline, and sufentanil 2 μg ml⁻¹ (5 ml) and ropivacaine 1 mg ml⁻¹ (20 ml) were administered. UtA-PI was measured before (T0), 30 min (T30), and 90 min (T90) after the first administration of epidural analgesic drugs, during both uterine relaxation and contraction.
Fifty-two patients were included in the study, 33 in the epidural group and 19 in the control. UtA-PI was significantly higher in the epidural compared with the control group, only at T30 and during contraction. There were no differences in the rate of oxytocin augmentation, mode of delivery, birth weight, and umbilical artery pH between the two groups.
Epidural analgesia using ropivacaine 1 mg ml⁻¹ (20 ml) significantly reduced placental blood flow only transiently during uterine contraction 30 min after the injection. These changes did not seem to affect neonatal outcomes.
A prospective randomized double-blind study comparing the dose-response curves of epidural ropivacaine for labor analgesia initiation between parturients with and without obesity
2024, Frontiers in Pharmacology

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ORIGINAL ARTICLEMinimum local analgesic concentrations of ropivacaine and levobupivacaine with sufentanil for epidural analgesia in labour

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Statistical analysis

Results

Discussion

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A randomized sequential allocation study to determine the minimum effective analgesic concentration of levobupivacaine and ropivacaine in patients receiving epidural analgesia for labor

Anesthesiology

ORIGINAL ARTICLE
Minimum local analgesic concentrations of ropivacaine and levobupivacaine with sufentanil for epidural analgesia in labour