Section Editor: Beth Glosten.
Epidural bupivacaine provides highly effective pain relief for labor and delivery, but limitations to its usefulness include motor blockade and cardiovascular toxicity. Motor block decreases maternal mobility and may prolong labor [1,2]. Maternal cardiac arrest and death have also been reported after an unintentional IV bupivacaine injection . Nevertheless, bupivacaine remains the most often used local anesthetic for labor analgesia.
In an attempt to reduce bupivacaine-induced side effects and toxicity, ropivacaine was developed. Ropivacaine is similar to bupivacaine in structure and anesthetic properties, but it is less cardiotoxic in animals . Ropivacaine may also be more selective for sensory fibers compared with other local anesthetics, producing less motor block [5-7]. These properties suggest that ropivacaine could be superior to bupivacaine in obstetric analgesia. Studies in obstetric patients undergoing cesarean section with 0.5% ropivacaine have shown no adverse maternal or fetal effects [8,9]. Similarly, labor epidural studies using 0.25% ropivacaine solutions lacked harmful maternal and neonatal effects and provided analgesia as effective as 0.25% bupivacaine [10,11].
The labor epidural studies published to date have used 0.25% ropivacaine solutions; however, dilute local anesthetic solutions (0.125%) are more often used for labor. Furthermore, previous studies administered ropivacaine by either intermittent bolus or continuous infusions set at predetermined rates [10,12,13]. With this design, it is likely that some of the patients studied received more local anesthetic than needed for comfort. Patient-controlled epidural analgesia (PCEA) can better match local anesthetic administration to patient need [14,15]. PCEA infusions adjust for individual pain thresholds, allowing patients to use only what local anesthetic they need to control pain. There have been no PCEA ropivacaine studies published. The purpose of this study, therefore, was to assess the potential benefits and potency of 0.125% ropivacaine compared with 0.125% bupivacaine in laboring patients using PCEA.
After obtaining institutional approval, ASA physical status I or II women with term, singleton, vertex pregnancies in active labor (cervical dilation 3-6 cm) requesting epidural analgesia were eligible for study inclusion. Exclusion criteria included weight more than 115 kg, inability to understand English, administration of IV analgesics within 1 h of epidural request, or allergy to local anesthetics. For epidural administration, patients in the sitting position had multiport catheters (B. Braun Medical, Bethlehem, PA) inserted 4 cm in the L2-3 or L3-4 epidural space. After a negative 2-mL subarachnoid and 5-mL IV test dose of 2% lidocaine, patients with adequate analgesia were asked to participate in the study. Patients not developing adequate analgesia after 7 mL of 2% lidocaine were excluded.
Informed consent was obtained, and patients were prospectively randomized by using a computergenerated list. In a double-blind study design, patients received 0.125% ropivacaine or bupivacaine by continuous PCEA infusion (Graseby 3300 PCA Pump; Graseby Medical LTD, Watford, UK). Basal infusion rates of 6 mL/h were supplemented with patientcontrolled boluses of 5 mL, available every 10 min with a 30-mL/h limit. For inadequate analgesia, anesthesia personnel administered 10-mL boluses of study solution until patient comfort was achieved.
Parturients reported pain intensity on a verbal scale (0 = no pain, 10 = worst pain) before epidural placement, 20 min after the 2% lidocaine test doses, and at 2-h intervals up to and including vaginal delivery or decision for cesarean section. Sensory levels to pinprick and degree of motor blockade were measured at the same time intervals (0 = can raise lower extremity off bed, 1 = able to bend knees and ankles, 2 = unable to bend knee, 3 = unable to bend ankle).
The mode of delivery was recorded as spontaneous, forceps-assisted, or cesarean section. If additional perineal anesthesia was needed for delivery, patients received 10-15 mL of either 2% or 3% 2-chloroprocaine. Neonates were assessed by 1- and 5-min Apgar scores. The study was terminated at the time of vaginal delivery or when the decision was made for cesarean section. At study termination, patients were asked to rate overall epidural analgesia as either excellent, good, fair, poor, or absent.
Automated maternal blood pressure and heart rate, tocodynomometry, and fetal heart rate were monitored throughout labor. Hypotension, defined as systolic blood pressure below 100 mm Hg, was treated with left uterine displacement, IV fluid, or ephedrine, as indicated.
Statistical analysis included Wilcoxon ranked sum, chi squared, Fisher's exact, and Student's t-tests, as appropriate. P < 0.05 was considered significant. Results are expressed as mean +/- SD unless otherwise stated. Group size was determined by power analysis (beta = 0.8, alpha = 0.05) to detect a 25% difference in ropivacaine use compared with bupivacaine control.
Fifty-one patients completed the study: 26 received ropivacaine and 25 received bupivacaine. The groups did not differ demographically (Table 1). Sixty-one patients enrolled in the protocol; however, 10 patients were eliminated for the following reasons: accidental epidural catheter removal (1 in bupivacaine group), inadequate analgesia with protocol deviation (2 in ropivacaine group, 3 in bupivacaine group), or incomplete data collection (1 in ropivacaine group, 3 in bupivacaine group).
Analgesia and Epidural Characteristics
There were no differences between groups with respect to local anesthetics use (Table 2). The mean total dose of ropivacaine was 98.5 +/- 51.4 mL (123 +/- 64 mg/patient), range 32.7-248.5 mL. For bupivacaine, the mean total dose was 78.6 +/- 36.5 mL (98 +/- 46 mg/patient), range 34.2-185.0 mL. Verbal pain scores (0-10) were similar between groups at all time intervals: 8.7 +/- 0.3 and 8.6 +/- 0.3 before epidural analgesia and 2.2 +/- 0.4 and 2.0 +/- 0.3 after epidural analgesia for bupivacaine and ropivacaine, respectively. There were no differences between groups in the number of patient-directed pump demands, pump doses delivered, or the number of patients receiving supplemental boluses of study solution by anesthesia care providers for labor and delivery (Table 2). The number of patients reporting good or excellent analgesia was also similar between groups (Table 2). None of the 51 patients completing the study reported poor analgesia.
The upper segmental level of analgesia to pinprick did not differ between groups. The median sensory levels achieved at interval evaluation are shown in Table 1. The degree of motor block was also similar between groups (Table 1). Motor block was mild (score of 0 or 1) in most patients and did not differ with ropivacaine or bupivacaine treatment. Some patients developed motor block associated with the lidocaine loading dose, but this was minimal (score of 0 or 1) in most patients and similar between groups.
Labor and Delivery Characteristics
The duration of labor and pitocin use did not differ between the groups (Table 1). There was no correlation with the use of pitocin and parity. Of the 12 primiparous patients in the ropivacaine group, 5 received pitocin, compared with 3 of 14 patients in the bupivacaine group. In multiparous patients, 2 of 14 patients in the ropivacaine group were administered pitocin during labor compared with 3 of 11 patients receiving bupivacaine.
The number of vaginal, instrumental, and cesarean deliveries was similar between groups (Table 1). We made no attempt to control for instrumental deliveries; the use of low or outlet forceps in our institution varies with obstetrical practice patterns. Mid-forceps delivery was not used in either group. The indications for cesarean section included failed trial of labor after previous cesarean section (two in ropivacaine group, one in bupivacaine group), cephalopelvic disproportion (two in ropivacaine group, three in bupivacaine group).
Apgar scores were similar between groups. One infant in each group had a 1-min Apgar score of less than 7, but by 5 min, Apgar scores were more than 7 in all infants.
Mild hypotension was the predominant local anesthetic effect observed in the study. There were no differences between the groups in the severity of hypotension or in the treatment rendered. Systolic blood pressure did not fall below 85 mm Hg in any patient. Eight patients in the ropivacaine group required IX ephedrine (5- to 10-mg bolus) for mild hypotension, compared with six patients in the bupivacaine group; all patients responded well to treatment.
The results of this study show that 0.125% ropivacaine, when given by PCEA infusion, is as effective as 0.125% bupivacaine for labor analgesia. At the 0.125% concentration used, we found ropivacaine and bupivacaine to be clinically indistinguishable; there were no significant differences in verbal pain scores, the amount of local anesthetic used, sensory levels, degree of motor blockade, or patient satisfaction.
Initial reports that ropivacaine produces less cardiovascular toxicity and motor blockade than bupivacaine offered promise that ropivacaine might be superior to bupivacaine for use in obstetrics [4,6,7]. Indeed, in laboratory studies with isolated nerve preparations, ropivacaine produced a much greater dissociation of sensory to motor block than did bupivacaine . This finding was predictable based on the lower lipid solubility of ropivacaine compared with bupivacaine and a more limited penetration of larger, myelinated nerve fibers, which convey motor impulses. Clinical studies, however, have not consistently found differences in motor block between the two drugs, and the potency of ropivacaine relative to bupivacaine remains unclear. Several studies in human volunteers have shown motor blockade to be less intense and shorter in duration with epidural ropivacaine compared with bupivacaine [7,16]. Similarly, for cesarean section, motor block was slower to develop and resolved more quickly when patients received 0.5% epidural ropivacaine compared with 0.5% bupivacaine [8,9]. Other than a potentially faster recovery room discharge, the benefits of limited motor blockade in surgical patients receiving epidural ropivacaine are uncertain. The benefits of having limited motor block in laboring patients, however, are better defined. Motor block has been associated with maternal dissatisfaction, longer labor, and more instrumental and surgical deliveries [1,2,17]. To date, labor epidural studies using 0.25% ropivacaine or bupivacaine have shown no difference in the magnitude of motor block [10,12,13]. Thus, the separation of sensory to motor blockade reported with ropivacaine may be clinically apparent only at higher concentrations.
Likewise, we found no decrease in motor block in patients receiving 0.125% ropivacaine. The motor blockade scoring system used in this study, however, is 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 anesthesia providers. We selected the current method because it is simple and clinically useful in detecting gross differences in motor block. Differences less than those observed by this scoring system may be clinically irrelevant.
Possible confounding factors in this study were the use of 2% lidocaine for the initial epidural test dose and the use of 2-chloroprocaine for delivery. We chose to administer lidocaine for several reasons. First, the effectiveness of ropivacaine as an intrathecal or intravascular test is unknown. Second, a 5-mL IV test bolus of 0.125% study solution may be too dilute to reliably produce the typical central effects (metallic taste, perioral numbness, and so on) observed with more concentrated local anesthetics. Third, we wanted to confirm adequate analgesia before patient inclusion in the study to minimize the subsequent need for epidural catheter manipulation and redosing because of poor block uniformity. It is our experience that 2% lidocaine 7 mL (140 mg) reliably produces adequate analgesia when the epidural catheter is properly inserted. Even if lidocaine administration affected initial motor block and sensory levels, all patients in each group received lidocaine. Furthermore, because the analgesia from a bolus administration of lidocaine is of moderate duration and the average duration from epidural catheter placement until delivery in this study was approximately five hours, it is unlikely that lidocaine administration adversely affected overall outcome. Likewise, 2-chloroprocaine administration did not adversely affect study outcome. This labor study was designed to examine the analgesic efficacy of dilute concentrations of ropivacaine and bupivacaine during labor, not delivery. Our primary goal for delivery was patient comfort; thus, 2-chloroprocaine was administered as needed and not controlled by study protocol. Therefore, we did not assess or report pain scores at delivery, only the percentage of patients requiring supplemental 2-chloroprocaine for delivery.
Although we obtained Apgar scores, we did not directly assess the effect of ropivacaine on the fetus. However, there were no significant fetal heart rate abnormalities noted throughout labor in any patient. Traditionally, neonatal status has been evaluated by Apgar scores and umbilical cord acid-base measurements. These measurements, however, do not distinguish between possible drug effects on a neonate and in utero asphyxia; the Amiel-Tison neonatal neurobe-havioral scoring system has been developed for this purpose . Although we did not use a neurobehavioral assessment in this study, other studies administering larger doses of ropivacaine for labor have used it to show no difference in neonatal outcome when mothers have been administered epidural ropivacaine compared with bupivacaine [10-12]. It is therefore doubtful that differences in neonatal neurobehavioral assessment or adverse effects from ropivacaine would have been discovered in this study by using lower concentrations.
In summary, we found 0.125% ropivacaine and 0.125% bupivacaine to be clinically indistinguishable. There were no differences in pain scores, amount of local anesthetic used, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction between the local anesthetics using PCEA for labor analgesia; both were highly effective. The reported benefits of ropivacaine (lower cardiovascular toxicity and motor blockade) may be more apparent when using higher local anesthetic concentrations. We found no benefits to using ropivacaine compared with bupivacaine for labor analgesia with dilute local anesthetic solutions.
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