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© 2001 International Anesthesia Research Society
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Abstract |
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We performed a randomized, double-blinded study to compare levobupivacaine with racemic bupivacaine for labor analgesia. Eighty term parturients received either levobupivacaine 0.125% or racemic bupivacaine 0.125%, to which was added sufentanil 0.75 µg/mL and epinephrine 1.25 µg/mL. As part of a combined spinal-epidural procedure, 2 mL of this mixture was initially injected intrathecally, and the same solutions were subsequently administered epidurally. For both combinations, onset until the first painless contraction was 4 to 5 min. Most patients were pain free during the second contraction. The duration of initial spinal analgesia was 93.5 ± 20 min and 94.7 ± 31 min for levobupivacaine and racemic bupivacaine, respectively. The duration of analgesia for the first epidural top-up dose was also similar in the two groups. Total local anesthetic requirements during labor were not different. The only major difference observed was the absence of motor impairment in levobupivacaine-treated parturients as compared with the Racemic Bupivacaine group, in which the incidence of a Bromage-1 motor block was 34%. Other side effects and obstetric or neonatal outcomes were not different between groups. Intrathecal levobupivacaine has a similar clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.
IMPLICATIONS: When used intrathecally and epidurally for labor analgesia, levobupivacaine had the same clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.
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Introduction |
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The intrathecal route for labor analgesia provides excellent pain relief of rapid onset. Different drugs and combinations have been used, ranging from opioids alone to multiple combinations containing bupivacaine, an opioid, clonidine, epinephrine, and neostigmine (1,2). The local anesthetic that has been used most extensively is bupivacaine, in doses ranging from 1 to 2.5 mg, and these doses, when combined with opioids, have provided analgesia without development of motor weakness or hemodynamic instability (3,4).
The newer local anesthetics are significantly less cardiotoxic and neurotoxic than bupivacaine (5,6). Although toxicity may be less important for the spinal component of a combined spinal-epidural (CSE) procedure, when proceeding with the epidural catheter for the remaining part of labor, cesarean delivery, and subsequent pain relief, less toxic compounds may be desirable. Levobupivacaine, a new amide local anesthetic, seems to be equally as potent as racemic bupivacaine, but some studies have found a trend toward differences in onset and duration of sensory or motor block (7–11).
For many years we have used our standard epidural mixture containing bupivacaine 0.125%, sufentanil 0.75 µg/mL, and epinephrine 1:800,000 for both the spinal and epidural components of CSE labor analgesia, but we have concerns regarding the potential for motor block and toxicity. The aim of this study was to compare the duration and quality of analgesia, as well as the side effects between bupivacaine and levobupivacaine, combined with sufentanil and epinephrine when administered via the spinal and epidural routes as part of CSE labor analgesia.
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Methods |
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After approval by the hospital ethics committee and obtaining written informed consent, 80 full-term parturients with vertex presentation in early labor (i.e., cervical dilation <5 cm) were randomly assigned to receive in a double-blinded fashion either levobupivacaine 0.125% + sufentanil 0.75 µg/mL + epinephrine 1:800,000 (L group) or bupivacaine 0.125% + sufentanil 0.75 µg/mL + epinephrine 1:800,000 (B group) for spinal and epidural analgesia. Two milliliters of this mixture was injected intrathecally, whereas subsequent epidural top-ups consisted of a 10-mL bolus without test dose.
The anesthetic procedure was initiated when the visual analog scale score (0–10) was more than 5. The CSE procedure was performed with the BD-Adjustable Durasafe combination needle (BD, Franklin Lakes, NJ). Patients were placed in the left lateral decubitus position, and after skin infiltration at the L3-4 or L4-5 interspace, a 17-gauge Tuohy needle was introduced by using a loss of resistance to air technique. After introduction of a 27-gauge Whitacre spinal needle and intrathecal injection, a 20-gauge multiorifice catheter was inserted in the epidural space. The interval between the spinal injection and the first painless contraction was measured. When analgesia was insufficient, i.e., when visual analog scale (0–10) score did not become <3 after 10 min, supplemental epidural boluses of 4 mL were administered. The time between the achievement of complete analgesia and the reappearance of pain was considered the duration of analgesia. Also, the duration of analgesia obtained with the first epidural top-up (10-mL bolus without test dose) was registered.
Within the first 20 min after each injection, vital variables were recorded every 5 min and thereafter at 30-min intervals. Hypotension, defined as a systolic blood pressure <95 mm Hg or a decrease of >25%, was corrected with IV ephedrine, administered in 5-mg increments. Before and 20 min after the spinal injection, motor block was assessed bilaterally by using a modified Bromage scale (0 = none; 1 = unable to lift a straight leg for 5 s; 2 = unable to flex a knee; 3 = unable to move the ankle joint). Distal proprioception, registered before and 20 min after the block, was measured by flexion/extension of the second, third, or fourth toe, bilaterally (four times), while the parturient kept her eyes closed. One wrong answer was regarded as a proprioceptive deficit. Patients were also asked to assess whether perineal squeezing was preserved, decreased, or impossible. Sedation and pruritus (four-point verbal rating) were scored at all check-up moments. Any episode of nausea or vomiting throughout the study period was registered.
Fetal heart rate (FHR) and uterine contractions were continuously monitored. Obstetric outcome, neonatal weight, Apgar scores at 1, 5, and 10 min, and umbilical artery pH values were also recorded.
Statistical analysis was performed by using the unpaired Student’s t-test for demographic data, time intervals, and doses, whereas for the nonparametric data a Fisher’s exact test was selected. A P < 0.05 value was considered as statistically significant.
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Results |
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There were no differences in patient demographics (Table 1). Three patients in the L group and two patients in the B group required epidural supplementation despite partial analgesia (four patients received 4 mL and one patient 8 mL). These patients were excluded because it would be impossible to distinguish between both routes with regard to the duration of analgesia and the incidence of side effects. All other parturients obtained complete pain relief. One patient in the L group and three in the B group delivered without an epidural top-up dose.
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Onset to the first painless contraction was identical in both groups (Table 2). Most patients were pain free after 4–5 min and continued to feel an average of two contractions after the spinal injection. The duration of analgesia, after the administration of the spinal drug, was not different and exceeded 1.5 h. The first epidural top-up revealed a duration exceeding 100 min without any apparent difference between the two drugs. Because only a few patients in each group required more than one epidural top-up, comparisons were made only for the first epidural top-up. The upper sensory level was identical in both groups and ranged between T3 and T11.
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None of the patients had motor impairment, proprioceptive deficit, or squeezing problems before the anesthetic procedure was started. At 20 min after the spinal injection, significantly more patients in the B group had a Bromage-1 motor block (Table 3). In addition, more patients in this group had a subjective impairment of perineal squeezing. Proprioceptive deficit was not different between the two groups. No motor block was registered after the first epidural top-up.
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Hypotension requiring ephedrine treatment was observed in two patients, both in the B group. None of the patients experienced more than slight sedation after the spinal injection. After the first epidural top-up, only one parturient, of the L group, experienced moderate sedation. One patient in each group vomited. Pruritus was the most common side effect (63% and 55%), although it was usually mild and never required treatment.
The incidences of labor induction or oxytocin augmentation were comparable in both groups (Table 4). Fetal bradycardia within the first 10 min after the spinal injection was registered in six patients of each group, but none required emergency cesarean delivery. In the L group, in four of these patients it was associated with uterine hypertonia, which necessitated tocolysis in two of them. Three patients of the six in the B group had uterine hypertonia as well, but tocolysis was not required. Instrumental delivery, cesarean delivery rate, neonatal birth weights, Apgar scores, and umbilical artery pH values were similar for both groups. All cesarean deliveries were performed after at least one epidural top-up dose was administered.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study demonstrates that there is no difference in analgesic effects between equal doses of racemic bupivacaine and levobupivacaine when used for labor analgesia via a CSE technique. Motor impairment seemed to be less with levobupivacaine, but no other differences were noticed.
The new and less toxic local anesthetics may enhance the safety of labor analgesia and anesthesia for operative deliveries as compared with racemic bupivacaine. Although it has been suggested that ropivacaine might induce less motor block than bupivacaine and thus might decrease the incidence of instrumental delivery (12), D’Angelo (13), reviewing 66 studies, found that only 16 of them were able to demonstrate motor block differences. Furthermore, of the 11 labor studies evaluated, only 2 found less motor impairment with ropivacaine. In addition, two independent studies have reported a 40% potency difference between ropivacaine and bupivacaine after up-down sequential allocation (14,15). Two clinical intrathecal studies confirmed that ropivacaine required at least a 50% larger dose than bupivacaine to obtain the same quality of sensory block (16,17). This may require rethinking of former ideas about decreased toxicity and motor impairment induced by ropivacaine.
Using a similar up-down sequential allocation design with levobupivacaine, Lyons et al. (7) found only a 2% difference in potency as compared with racemic bupivacaine. Therefore, changing from bupivacaine to levobupivacaine may not require changing of dosage schedules. However, possible differences in onset and duration of sensory block, as well as the degree and duration of motor block (9–11), are controversial. In addition, it has been suggested that 0.5% levobupivacaine, i.e., 5 mg/mL, will contain 13% more local anesthetic than 0.5% racemic bupivacaine, because this corresponds with milligrams of bupivacaine-hydrochloride per milliliter (18).
For intrathecal labor analgesia, bupivacaine 1 to 2.5 mg is still the "gold standard" (1–4). Although these doses allow safe ambulation, Nickells et al. (19) showed that bupivacaine 2.5 mg caused more motor block than 12.5 mg epidural bupivacaine.
The intrathecal use of levobupivacaine for relief of labor pain has not been reported. The few labor studies performed with this new local anesthetic have compared epidural bolus doses with 0.25% or continuous epidural infusion with the 0.125% concentration (9,10). The quality and duration of analgesia was found to be similar between bupivacaine and levobupivacaine, but a trend was noticed toward less motor impairment with levobupivacaine as well.
This study also suggests that levobupivacaine may cause less motor weakness than the racemic substance. Motor impairment may affect the quality of bearing down, but may also relax the pelvic muscles, causing abnormal fetal head descent and dystocia. Although this might increase the risk of instrumental and cesarean delivery (20), the motor block differences in this study did not affect obstetric outcome. We routinely ask our patients to rate their ability to squeeze their perineal muscles by means of a three-point verbal rating scale (21). Although this is admittedly an unvalidated assessment, we found that squeezing was subjectively impaired in more parturients receiving racemic bupivacaine, and it was considered impossible by eight parturients in this group versus none in the Levobupivacaine group.
Abnormalities with respect to the FHR and uterine contractility were similar in both groups. In an earlier study, we compared intrathecal sufentanil 7.5 µg with 1.5 mL of our standard epidural bupivacaine solution as used in this study (22). The incidence of nonreassuring FHR changes was significantly more frequent with the largest sufentanil dose. In the group receiving the small dose of sufentanil, this incidence was 12%, being consistent with the results of this study, and also less pruritus and a lower upper sensory level were registered. Recently, in a large retrospective study, Van de Velde et al. (23), comparing the same standard epidural mixture (2 mL intrathecally) with intrathecal sufentanil 7.5 µg or epidural analgesia throughout labor, were able to confirm the decreased incidence of nonreassuring FHR abnormalities with the small-dose combined regimen as compared with the larger dose of sufentanil alone. Despite a 12% incidence of nonreassuring FHR patterns in patients receiving the larger sufentanil dose, the cesarean delivery rate did not differ between the study groups.
Use of standard epidural solutions for both the spinal and epidural components of CSE labor analgesia offers the additional advantage that no special intrathecal mixtures need to be prepared. Limited drug handling may also reduce the risk of mixing errors, contamination, and wasting of drugs.
Although the sufentanil dose used in our patients was relatively small, it approximates the 50% effective dose measured in nulliparous women (24). However, the benefit of the very small epinephrine dose remains to be demonstrated.
In conclusion, this study demonstrates that levobupivacaine 0.125% and racemic bupivacaine 0.125%, in combination with a small dose of sufentanil and epinephrine, do not differ with respect to onset, duration, and quality of analgesia when used for both intrathecal and epidural labor analgesia. Slight motor impairment, however, seems to occur more often with use of racemic bupivacaine. Further studies are required to confirm that levobupivacaine causes less or shorter lasting motor impairment and thus might offer more clinical benefits than racemic bupivacaine.
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References |
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- Kartawiadi SL, Vercauteren MP, Van Steenberge AL, Adriaensen H. Spinal analgesia during labor with low-dose bupivacaine, sufentanil, and epinephrine: a comparison with epidural analgesia. Reg Anesth 1996; 21: 191–6.[Web of Science][Medline]
- Owen MD, Ozsarac O, Sahin S, et al. Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for early labor analgesia. Anesthesiology 2000; 92: 361–6.[Web of Science][Medline]
- Collis RE, Harding SA, Morgan BM. Effect of maternal ambulation on labour with low-dose combined spinal-epidural analgesia. Anaesthesia 1999; 54: 535–9.[Web of Science][Medline]
- Campbell DC, Camann W, Datta S. The addition of bupivacaine to intrathecal sufentanil for labor analgesia. Anesth Analg 1995; 81: 305–9.[Abstract]
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Morrison SG, Dominguez JJ, Frascarolo P, Reiz S. A comparison of the electrocardiographic cardiotoxic effects of racemic bupivacaine, levobupivacaine, and ropivacaine in anesthetized swine. Anesth Analg 2000; 90: 1308–14.
[Abstract/Free Full Text] - Huang YF, Pryor ME, Mather L, et al. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 1998; 86: 797–804.[Abstract]
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Lyons G, Columb M, Wilson RC, et al. Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine. Br J Anaesth 1998; 81: 899–901.
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Burke D, Henderson DJ, Simpson AM, et al. Comparison of 0.25% S(-) bupivacaine with 0.25% RS-bupivacaine for epidural analgesia in labour. Br J Anaesth 1999; 83: 750–9.
[Abstract/Free Full Text] - Convery P, Burke D, Donaldson L, et al. Comparison of 0.125% levobupivacaine and 0.125% bupivacaine epidural infusions for labour analgesia. Br J Anaesth 1999; 82S: S163.
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Cox CR, Faccenda KA, Gilhooly C, et al. Extradural S(-)-bupivacaine: comparison with racemic RS-bupivacaine. Br J Anaesth 1998; 80: 289–93.
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[Abstract/Free Full Text] - D’Angelo R. Are the new local anesthetics worth their price? Acta Anaesthesiol Scand 2000; 44: 639–41.[Web of Science][Medline]
- Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor. Anesthesiology 1999; 90: 944–50.[Web of Science][Medline]
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[Abstract/Free Full Text] - Gautier P, De Kock M, Van Steenberge A, et al. Intrathecal ropivacaine for ambulatory surgery. Anesthesiology 1999; 91: 1239–45.[Web of Science][Medline]
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[Abstract/Free Full Text] - Schug SA. Correction factor for comparisons between levobupivacaine and racemic bupivacaine [letter]. Reg Anesth Pain Med 2001; 26: 91.[Medline]
- Nickells JS, Vaughan DJ, Lillywhite NK, et al. Speed of onset of regional analgesia in labour: a comparison of the epidural and spinal routes. Anaesthesia 2000; 55: 17–20.[Web of Science][Medline]
- Thorp JA, Hu D, Albin R, et al. The effects of intrapartum epidural analgesia on nulliparous labor: a randomized prospective trial. Am J Obstet Gynecol 1993; 169: 851–8.[Web of Science][Medline]
- Vercauteren MP, Jacobs S, Jacquemyn Y, Adriaensen H. Intrathecal labor analgesia with bupivacaine and sufentanil: the effect of adding 2.25 microgram epinephrine. Reg Anesth Pain Med 2001; 26: 472–7.
- Vercauteren M, Bettens K, Van Springel G, et al. Intrathecal labor analgesia: can we use the same mixture as is used epidurally? Int J Obstet Anesth 1997; 6: 242–6.[Medline]
- Van de Velde M, Vercauteren M, Vandermeersch E. Fetal heart rate abnormalities following regional anesthesia for labor pain: the effect of intrathecal opioids. Reg Anesth Pain Med 2001; 26: 257–62.[Web of Science][Medline]
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