Bupivacaine continues to be the most widely used local anesthetic for epidural labor analgesia because it provides excellent sensory block during labor and delivery (1). However, limitations to its usefulness include the potential for motor blockade and central nervous system (CNS) and cardiac toxicity. Its use in increasingly smaller concentrations has drastically reduced the risk of these complications. Nevertheless, new drugs are now being developed that, given their pharmacological characteristics, may become alternatives to bupivacaine for labor analgesia.
Ropivacaine, the S-enantiomer of 1-propyl-2′6′pipecol- oxylidide, is an amide local anesthetic with a chemical structure related to mepivacaine and bupivacaine. A number of studies suggest that ropivacaine is associated with less CNS and cardiac toxicity (2,3) and produces less motor block than bupivacaine (4–6). Since its introduction, several authors have compared its efficacy in obstetric analgesia with that of bupivacaine (1,7–12). Until now, the two local anesthetics have been compared at the same concentration because it was assumed that they were equipotent. However, one recent study suggests that bupivacaine is more potent than ropivacaine (13).
Polley et al. (14) calculated the relative potencies of bupivacaine and ropivacaine by using an up-down sequential allocation study design. The authors concluded that ropivacaine was significantly less potent than bupivacaine, with a potency ratio of 0.6. Our study was designed to compare the analgesic efficacy and degree of motor block produced by 0.0625% bupivacaine plus fentanyl 2 μg/mL with 0.1% ropivacaine plus fentanyl 2 μg/mL. We compared these solutions because they are often used clinically and have approximately a 0.6 ratio. According to the results reported by Polley et al. (14), these two anesthetic solutions should provide the same analgesic effectiveness.
The protocol of this prospective study was approved by the ethics committee of our center and written informed consent was obtained from each patient. The inclusion criteria included active labor, cervical dilation ≤5 cm, single fetus, vertex presentation, and request for epidural analgesia. Multiparous women who had undergone cesarean delivery for the first delivery were considered nulliparous. Exclusion criteria included ASA physical status ≥3, age <18 yr, administration of parenteral analgesia before the epidural injection, inability to understand Spanish, or when delivery was expected to have a duration of <1 h.
After administration of 1000 mL of Ringer’s lactate solution, with the parturients seated or in the lateral decubitus position, an epidural catheter (Perifix®, B. Braun, Melsungen AG, Germany) was inserted at the L3-4 or L2-3 interspace. A test dose of 2.5 mL of 2% lidocaine with epinephrine was used to exclude intravascular or subarachnoid placement. An 8-mL bolus of 0.7% lidocaine (without epinephrine) and 50 μg of fentanyl was subsequently administered. If adequate analgesia was achieved after this bolus, the patient was randomly assigned to one of the two groups according to a computer-generated list. Continuous infusion of a solution of either 0.0625% bupivacaine with fentanyl 2 μg/mL (Group B) or 0.1% ropivacaine plus fentanyl 2 μg/mL (Group R) was then begun at a rate of 15 mL/h (IVAC 598 volumetric pump; Alaris Medical Systems, San Diego, CA). The study ended at the time of vaginal delivery, assisted or not, or when the decision was made to perform a cesarean delivery. If additional anesthesia was needed for assisted delivery or if birth was by cesarean delivery, patients were anesthetized at the discretion of the attending anesthesiologist. Both the patient and the anesthesiologist who delivered analgesia were blinded as to the study solutions.
Pain intensity was measured using a verbal scale of 0 to 10 points (0 = no pain, 10 = worst pain) before administration of epidural analgesia and 5, 10, 20, 30, 60, and 120 min after the first dose of 0.7% lidocaine, and every 90 min thereafter until the end of the study. Scores of ≤2 were considered satisfactory. When the women who were receiving an epidural infusion complained of pain, a 5-mL bolus of the analgesic solution was administered every 10 min until pain score was ≤2. The total number of boluses required during the first and second stages of labor was recorded.
The degree of motor block was assessed according to a modified Bromage scale (0 = complete motor blockade–inability to move feet or knees; 1 = the patient is able only to move the feet; 2 = able to move the knees; 3 = detectable weakness of hip flexion; 4 = no detectable weakness while supine). Cephalad levels of sensory block were evaluated by temperature changes using alcohol swabs; if the levels of sensory block on the right and left sides differed, the higher of the two was recorded. Hypotension, defined as a decrease in the systolic arterial pressure below 90 mm Hg, was managed with left uterine displacement, accelerating IV fluid administration, or with 5–10 mg ephedrine boluses. The level of sensory block, degree of motor block, and arterial blood pressure were assessed at the same time as the degree of analgesia. Maternal oxyhemoglobin saturation and heart rate were monitored by pulse oximetry for 10 min after initial injection. All episodes of nausea, vomiting, somnolence, and pruritus were also recorded.
Fetal heart rate and uterine activity were monitored continuously throughout labor by using cardiotocography. The duration of labor, mode of delivery (spontaneous, forceps-assisted, cesarean delivery), 1-min and 5-min Apgar scores, and umbilical artery pH were registered. Overall quality of epidural analgesia was judged by patients after delivery as excellent, good, fair, or poor.
Statistical analysis of the data included χ2 test, with Yates’ correction when necessary, two-sided Student’s t-tests, and correlation coefficient, as appropriate. P < 0.05 was considered significant.
One hundred women were initially included in the protocol (52 receiving bupivacaine, 48 receiving ropivacaine). Two patients (one in each group) were later excluded because of protocol deviation. There were no differences between the groups with respect to demographic and labor characteristics (Table 1).
The verbal pain score was similar in the two groups for each time point at which it was evaluated. Before epidural injection, the mean scores were 7.9 ± 1.6 in Group B and 8.2 ± 1.6 in Group R (P = 0.4); after administration of analgesia, these values were 1.04 ± 1.63 and 0.95 ± 1.71, respectively (P = 0.493). Both groups showed a significant, but weak, correlation between the number of boluses and the duration of labor, with very similar correlation coefficients (Group B:r = 0.33; Group R:r = 0.24). There were no significant differences in the number of boluses administered during the first and the second stages of labor (Table 2). Patients’ evaluations of their labor and delivery analgesia were similar in both groups (Table 2). None of the women judged the analgesia to be poor.
There were no differences between the two groups in terms of the levels of sensory block obtained. The mean levels reached at the different time points are shown in Table 2.
The degree of motor block was similar at all time intervals at which it was assessed (Table 2). After 60 min (the estimated time required for the action of the initial lidocaine bolus to take effect) five women in Group B (9.8%) and three in Group R (6.3%) presented some degree of motor block (defined as ≤3 according to the modified Bromage scale). These differences were not statistically significant.
The number of spontaneous, forceps-assisted, and cesarean deliveries were similar in the two groups (Table 3). There were no significant differences in the 1-min and 5-min Apgar scores or umbilical artery pH (Table 3).
There were no differences with regard to hemodynamic stability. Two patients in Group B and one in Group R received ephedrine; all three responded well to the treatment. In all, 31.3% of the women in Group B and 23.4% of those in Group R complained of pruritus, differences that were not statistically significant. Three women in each group presented with nausea and vomiting.
We compared different concentrations of epidural bupivacaine and ropivacaine for labor analgesia that were thought to be equipotent. The results demonstrate that 0.0625% bupivacaine and 0.1% ropivacaine are equally effective; we observed no significant differences in the verbal pain scores, number of boluses, levels of sensory block, degree of motor block, or patient satisfaction. These findings confirm that bupivacaine may be more potent than ropivacaine.
A number of studies have compared the analgesic efficacy of equal concentrations of bupivacaine and ropivacaine for obstetric epidural analgesia. Those comparing 0.25% bupivacaine with 0.25% ropivacaine revealed no significant differences in either the quality of analgesia or in motor block (7–11). The conclusions were similar when 0.125% concentrations were used; Owen et al. (1) compared 0.125% bupivacaine and ropivacaine using patient-controlled epidural analgesia, concluding that there were no significant clinical differences between the two. In a more recent study (12) the attempt was made to evaluate the differences observed after intermittent administration of 0.125% boluses of bupivacaine and ropivacaine, both combined with sufentanil. The results showed that ropivacaine plus sufentanil produced the same analgesia as bupivacaine plus sufentanil but with less motor block, although the reduced motor block was of no clinical importance and had no impact on the course of labor and delivery.
In all these reports, it was assumed that bupivacaine and ropivacaine were equipotent. However, studies on the relative potencies of these two analgesics are inconclusive, making it difficult to establish reliable conclusions from the comparison of their analgesic efficacy or toxicity profile. In the aforementioned study by Polley et al. (14), the relative potencies of bupivacaine and ropivacaine were estimated by using an up-down sequential allocation method to determine the minimum local analgesic concentration (MLAC) of the two substances. Up-down designs are open label, with each subsequent patient’s dose varied according to the previous patient’s response. The authors concluded that the MLAC of ropivacaine during the first stage of labor was 0.111%, whereas that of bupivacaine was 0.067% and, thus, that ropivacaine was significantly less potent than bupivacaine, with a potency ratio of 0.6. The model for calculating the MLAC was introduced by Columb and Lyons (15) to determine the analgesic potency of epidural local anesthetics during the first stage of labor, and it is defined as the median effective local analgesic concentration (EC50). It is similar to the concept of the minimum alveolar concentration of volatile anesthetics. Several other studies in which the same clinical model was used have resulted in comparable estimations of the EC50 of bupivacaine during labor (15–17). Somewhat larger EC50, however, have been found for bupivacaine in parturients (18,19) although these discrepancies are probably attributable to differences in the populations studied.
Our study demonstrates that after a lidocaine test dose, 0.0625% bupivacaine plus fentanyl 2 μg/mL and 0.1% ropivacaine plus fentanyl 2 μg/mL are clinically indistinguishable, which seems to confirm that ropivacaine is less potent than bupivacaine. The concentrations of both solutions are very similar to their theoretical EC50. Although the sample size of the study should be bigger to be sure that some type 2 error has not occurred, this does not lessen the clinical relevance of these findings.
The purpose of adding lipid-soluble opioids (in our series, fentanyl) is to improve the analgesic efficacy of the solutions without increasing motor block. Opioids reduce the EC50 of bupivacaine and ropivacaine in a dose-dependent manner. 1
The EC50 calculated according to the clinical model used by Polley et al. (14) provides no information regarding the slope or the shape of the dose-response curve or EC95. For example, although the EC50 of the two drugs differ, their dose-response curves may overlap at larger concentrations (14). In the aforementioned studies comparing bupivacaine and ropivacaine at concentrations of 0.125% or more, the absence of significant differences between the two was probably a result of the fact that these concentrations are much larger than their EC50, with doses located at the higher end of the analgesic dose-response curve (15). The differences between the two anesthetics would only be evident at concentrations near the EC50. Thus, in the study by Peres da Silva et al. 2 in which 0.07% bupivacaine was compared with 0.07% ropivacaine, both in combination with sufentanil, the preliminary results demonstrated that bupivacaine was significantly better for the management of labor and delivery pain.
Analgesic 2 requirements may increase as delivery nears. In fact, the MLAC increases as labor progresses (17). In the present work, we found no differences in the verbal pain score at any of the time points at which it was assessed. Likewise, the number of boluses needed to relieve the pain was similar in the two groups throughout both the first and second stages of labor.
The degree of motor block during epidural analgesia depends not only on the drug used, but also on the cumulative dose of the local anesthetic. That is, the impact on motor function may increase progressively in relation to the duration of labor. Russell and Reynolds (20) demonstrated the presence of motor block in a group of parturients who received an infusion of 0.0625% bupivacaine plus an opioid. Twenty percent of the women were unable to raise their legs after 4–6 hours of infusion. In the present study, the motor block was similar in the two groups throughout labor and delivery. Although the Bromage scale is not a highly sensitive method, it probably detects differences in the degree of motor block when they are relevant. The differential block attributed to ropivacaine may be attributable more to its lower potency than to an intrinsic effect of the anesthetic itself.
The use of lidocaine may distort the results of the study. However, the decision was made to administer the test dose and initial bolus of lidocaine, as did Owen et al. (1) in their study, for two reasons. First, the objective of the study was to compare bupivacaine and ropivacaine in analgesic solutions, not as an initial dose; lidocaine enabled us to ensure that the analgesia was adequate before including the patients in the study. Second, because an 8-mL bolus of 0.7% lidocaine produces an effect of moderate duration, its influence on the overall analgesia and motor block during labor and delivery (having a mean duration of 384 minutes) is improbable.
In conclusion, 0.0625% bupivacaine plus fentanyl 2 μg/mL and 0.1% ropivacaine plus fentanyl 2 μg/mL were equally effective in achieving adequate analgesia with minimum motor block. These findings suggest that there are no advantages to the use of epidural ropivacaine for labor analgesia because highly diluted concentrations of bupivacaine plus an opioid reduce the risk of cardiovascular toxicity and the degree of motor block, are equally effective as ropivacaine, and are less expensive.
1 Pratt SD, Sarna MC, Soni AK, et al. The effective concentration (EC50) of ropivacaine with fentanyl for labor epidural analgesia [abstract]. Anesthesiology 1997;87:A910.
2 Peres da Silva E, Abboud TK, Lee J. Comparison of 0.07% ropivacaine plus sufentanil and 0.07% bupivacaine plus sufentanil for epidural anesthesia during labor and delivery [abstract]. Anesthesiology 1997;87:A882.
1. Owen M, D’Angelo R, Gerancher JC, et al. 0.125% ropivacaine is similar to 0.125% bupivacaine for labour analgesia utilizing patient-controlled epidural infusion. Anesth Analg 1998; 86: 527–31.
2. Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563–9.
3. Knudsen K, Beckman Surkula M, Blomberg S, et al. Central nervous and cardiovascular effects of IV infusions of ropivacaine. Br J Anaesth 1997; 78: 507–14.
4. 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.
5. Feldman HS, Covino BG. Comparative motor blocking effects of bupivacaine and ropivacaine, a new amino amide local anesthetic, in the rat and dog. Anesth Analg 1988; 67: 1047–52.
6. 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.
7. Muir HA, Writer D, Douglas J, et al. Double-blind comparison of epidural ropivacaine 0.25% and bupivacaine 0.25% for the relief of childbirth pain. Can J Anaesth 1997; 44: 599–604.
8. 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.
9. McCrae AF, Jozwiak H, McClure JH. Comparison of ropivacaine and bupivacaine in extradural analgesia for relief of pain in labour. Br J Anaesth 1995; 74: 261–5.
10. Writer D, Stienstra R, Eddleston JM, et al. Neonatal outcome and mode of delivery after epidural analgesia for labour with ropivacaine and bupivacaine: a prospective meta-analysis. Br J Anaesth 1998; 81: 713–7.
11. Stienstra R, Jonker T, 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.
12. 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.
13. Tuttle AA, Katz JA, Bridenbaugh PO, et al. A double-blind comparison of the abdominal wall relaxation produced by epidural 0.75% ropivacaine and 0.75% bupivacaine in gynecologic surgery. Reg Anesth 1995; 20: 515–20.
14. Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labour: implications for therapeutic indexes. Anesthesiology 1999; 90: 944–50.
15. Columb MO, Lyons G. Determination of the minimum local analgesic concentrations of epidural bupivacaine and lidocaine in labour. Anesth Analg 1995; 81: 883–7.
16. Lyons G, Columb MO, Hawthorne L, Dresner M. Extradural pain relief in labour: bupivacaine sparing by extradural fentanyl is dose dependent. Br J Anaesth 1997; 78: 493–7.
17. Capogna G, Celleno D, Lyons G, et al. Minimum local analgesic concentration of extradural bupivacaine increases with progression of labour. Br J Anaesth 1998; 80: 11–13.
18. Polley LS, Columb MO, Wagner DS, Naughton NN. Dose-dependent reduction of the minimum local analgesic concentration of bupivacaine by sufentanil for epidural analgesia in labor. Anesthesiology 1998; 89: 626–32.
19. Capogna G, Celleno D, Lyons G, Columb MO. Determination of the minimum local analgesic concentration of epidural ropivacaine in labour [abstract]. Br J Anaesth 1998; 81: A506.
20. Russell R, Reynolds F. Epidural infusion of low-dose bupivacaine and opioid in labour: does reducing motor block increase the spontaneous delivery rate? Anaesthesia 1996; 51: 266–73.