Anesth Analg 2006;103:182-186
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000221038.46094.c0
OBSTETRIC ANESTHESIA
Section Editor:
David J. Birnbach
Levobupivacaine-Sufentanil With or Without Epinephrine During Epidural Labor Analgesia
Filiep M. Soetens, MD*,
Maurits A. Soetens, MD*, and
Marcel P. Vercauteren, MD, PhD
From the *Department of Anesthesiology, Sint-Elisabeth Hospital, Turnhout, Belgium; and Department of Anesthesiology, University Hospital Antwerp, Edegem, Belgium.
Address correspondence and reprint requests to Marcel P. Vercauteren, MD, PhD, Department of Anesthesiology, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium. Address e-mail to marcel.vercauteren{at}uza.be.
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Abstract
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In a prospective, randomized, double-blind study, we investigated whether epinephrine increased the efficacy of levobupivacaine and sufentanil during epidural labor analgesia. Seventy term parturients received an epidural injection of levobupivacaine 0.125% and sufentanil 0.75 µg/mL with or without 1:800,000 epinephrine. After an initial dose of 10 mL, a patient-controlled analgesia pump was started. Total and hourly drug consumption, pain scores using the visual analog scale, sensory and motor block, duration of labor, vital variables, maternal and neonatal outcome, and side effects were compared. If the parturients experienced insufficient pain relief during the study, even after a rescue dose of 10 mL, they were excluded from further study and received 10 mL of bupivacaine 0.125% and sufentanil 0.75 µg/mL with 1:800,000 epinephrine. Hourly drug consumption, rescue dosing, and pain scores at 15 min and 20 min were lower in the epinephrine group. The incidence of motor block and duration of the second stage of labor tended to be higher in the epinephrine group and were associated with lower Apgar scores at 1 and 5 min. These findings suggest that the addition of epinephrine intensifies the effects of epidural levobupivacaine and sufentanil but may cause more motor block.
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Introduction
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The addition of epinephrine to local anesthetics and/or opioids used for epidural analgesia during labor is the subject of much debate. Although epinephrine may prolong and intensify the analgesic action of local anesthetics and opioids, reduces the systemic absorption of local anesthetics and opioids, and can be used to detect intravascular injection, the addition of epinephrine has some limitations (1–3). Potential disadvantages include reduced stability of solutions containing epinephrine, decreased uterine blood flow and contractility, prolongation of labor, increased incidence of motor block, hypotension, pruritus, and nausea and vomiting (2,4,5).
One of the mechanisms of the beneficial action of epinephrine is local vasoconstriction with decreased systemic absorption of local anesthetics and opioids (3,6). Because levobupivacaine may have intrinsic vasoconstrictor properties, the addition of epinephrine may not be warranted (7). However, the intrinsic vasoconstrictor properties of small concentrations of levobupivacaine on the vasculature in the epidural space are not known.
The purpose of the present study was to investigate whether epinephrine decreased the total and hourly consumption of levobupivacaine and sufentanil and had an effect on the quality of analgesia, the severity of maternal side effects, and, finally, on the obstetrical and neonatal outcome.
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METHODS
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After approval by the hospital ethics committee of both participating centers and written informed consent, 70 parturients in active early labor (cervical dilation of <6 cm at the time of their request for analgesia) with a single, term (37 to 41 wk of gestation) fetus in vertex presentation, were included in this prospective, double-blind multicenter study. Parturients with hypersensitivity to amide local anesthetics or extremes of height (<155 cm and >180 cm) and weight (body mass index >32) were excluded.
Before initiation of epidural analgesia, IV intravascular fluid administration was initiated with 500 mL of 0.9% saline. The parturient was placed in the left lateral decubitus position and the epidural space was identified at the L3-4 or L4-5 interspace with a 16-gauge Tuohy needle using the loss-of-resistance to saline technique. A Portex multiorifice epidural catheter was inserted 4 cm into the epidural space.
Using a random number table and a sealed envelope technique, parturients were randomly assigned to receive in a double-blind fashion levobupivacaine 0.125% plus sufentanil 0.75 µg/mL with 1:800,000 (1.25 µg/mL) epinephrine (LSE group) or without epinephrine (LS group). The study solutions were prepared aseptically by an anesthesiologist not directly involved in the study (first center) or were prepared by the pharmacist as blinded vials (second center). Each center studied an equal number of parturients in each group. The initial loading dose of 10 mL of the study solution was given by hand between contractions over 30 to 45 s. The time of the injection of the initial loading dose was defined as time zero and assessments were scheduled accordingly. Patient-controlled epidural analgesia was started 20 min after the initial loading dose with a bolus dose of 4 mL, a lockout interval of 10 min and no background infusion. If at any time, there was insufficient pain relief after 2 subsequent boluses, a rescue dose of 10 mL of the study solution was given manually. If this was still not sufficient after 15 min, parturients received 10 mL of bupivacaine 0.125% and sufentanil 0.75 µg/mL with 1:800,000 epinephrine and were excluded from further study.
The total amount of study solution was recorded, except for parturients who had insufficient analgesia with the study solution and received 10 mL of bupivacaine 0.125% and sufentanil 0.75 µg/mL with 1:800,000 epinephrine and for those who delivered by cesarean section. In all parturients the hourly consumption of study solution was calculated. For the parturients with insufficient analgesia or who delivered by cesarean section, the time of administering 10 mL of bupivacaine 0.125% and sufentanil 0.75 µg/mL with 1:800,000 epinephrine or the moment of the decision to perform a cesarean section was taken as the endpoint to calculate the hourly consumption. The number of parturients who received one or more rescue doses of 10 mL with the study solution was also recorded.
Pain with contractions was assessed by a 100-mm visual analog scale (VAS) (where 0 mm represented no pain and 100 mm the worst imaginable pain) and was registered immediately before and 5, 10, 15, and 20 min after the initial loading dose. Subsequently, VAS scores were evaluated every hour after the start of the study until delivery and after episiotomy repair.
The extent of the sensory block was determined bilaterally by the perceived temperature difference to an ether swab after 20 min, every hour thereafter, and immediately before delivery.
The duration of the interval between the initial loading dose and delivery, mode of delivery (spontaneous, vacuum, forceps, or cesarean section), Apgar scores at 1 and 5 min, and neonatal weight were registered.
Twenty minutes after the start of the study, every hour, and immediately before delivery, the degree of motor blockade was assessed bilaterally by using a modified Bromage scale (0 = no motor blockade; 1 = unable to lift a straight leg for 5 s; 2 = unable to flex a knee; 3 = unable to move the ankle joint). If there was a difference in motor block between the two legs, the highest score was noted.
Fetal heart rate and uterine contractions were continuously monitored. Maternal arterial blood pressure and heart rate were measured before the initial loading dose, at 5, 10, and 20 min, every hour, and immediately before delivery. Signs and symptoms of aortocaval compression were treated by turning the parturient on the left side. If necessary, ephedrine was administered IV in 5-mg increments to treat hypotension. Throughout labor and delivery the occurrence of pruritus, nausea, vomiting, and shivering was assessed.
Based on previous results (8) we determined that for 
= 0.05, a sample size of 30 parturients in each group would confer a 80% power to detect a 20% difference in drug consumption. Allowing for withdrawals, 70 parturients were entered in the study. Statistical analysis was performed by using a two-tailed unpaired Student’s t-test for data expressed as mean ± sd, analysis of variance for repeated measurements followed by the Scheffe F-test as appropriate for pain score evaluation, whereas for nonparametric data the Fisher’s exact test was selected. A P < 0.05 value was considered statistically significant.
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RESULTS
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One parturient in the LSE group (intravascular catheter) and two in the LS group (unilateral block and protocol violation) were excluded from further analysis. Patient demographics did not differ between groups (Table 1).
The total drug consumption was 19% larger in the LS group (Table 2). Although this difference was not statistically significant, parturients in the LSE group required less study solution per hour (9 ± 3 mL/h versus 11 ± 4 mL/h; P = 0.03). The number of parturients requiring one or more rescue doses with study solution was 14 of 34 (41%) in the LSE group and 21 of 33 (64%) in the LS group (P = 0.06). The volume of rescue medication per individual parturient was significantly smaller in the LSE group (5 ± 7 mL versus 9 ± 9 mL; P = 0.02). One parturient in the LSE group and 4 parturients in the LS group had insufficient pain relief. All these parturients became pain free after 10 mL of bupivacaine 0.125% and sufentanil 0.75 µg/mL with 1:800,000 epinephrine.
The VAS pain scores were similar for both groups before initiating epidural analgesia. At 15 min and 20 min after the initial loading dose the VAS pain scores were significantly lower in the LSE group (Fig. 1). Twenty min after the initial loading dose, a bilateral sensory block up to T10 was not obtained in 4 of 34 parturients (12%) in the LSE group and in 11 of 33 parturients (33%) in the LS group (P < 0.05). At 60 min and 120 min pain scores were identical. The VAS pain scores during the second stage were also comparable between the two groups.
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Figure 1. Pain scores measured using a visual analog scale (0–10). The black and gray bars represent the LSE group and LS group respectively. LSE, levobupivacaine, sufentanil, epinephrine; LS, levobupivacaine, sufentanil. *P < 0.05.
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The interval between the initial loading dose and delivery was almost identical in both groups (Table 3). Although there was a trend towards a longer second stage of labor in the LSE group, this result was not statistically significant (64 versus 48 min; P = 0.15). The incidences of instrumental delivery and cesarean delivery were similar between the groups. Two parturients in the LSE group and 3 in the LS group required a delivery by cesarean section.
Apgar scores were lower in the LSE group. At 1 min they were 7 (range 3–9) versus 8 (range 6–10; P < 0.05) in the LS group while at 5 min these values increased to 8 (range 6–10) versus 9 (range 8–10; P < 0.01). The occurrence of values <7, either at 1 or 5 min, were similar in both groups (20% and 8% respectively, not significant).
The incidence of the highest Bromage score noticed during the study tended to be more frequent in the LSE group (50% versus 27%; P = 0.07) (Table 4). This was always a Bromage 1 score, except for one parturient in each group. The mean interval of the occurrence of motor block after the initial loading dose was 4 h and was similar in the two groups. There was no significant difference in maternal and fetal heart rate, the incidence or severity of maternal hypotension requiring ephedrine, and in the occurrence of other side effects between the two groups.
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DISCUSSION
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The present study demonstrates that the addition of epinephrine to levobupivacaine and sufentanil decreases the hourly consumption of the levobupivacaine and sufentanil and provides faster maternal comfort during epidural labor analgesia. However, Apgar scores at 1 minute and 5 minutes were lower.
It has been known for more than half a century that epinephrine, injected in the epidural or spinal space, produces an antinociceptive effect (9). During the administration of epidural labor analgesia, the addition of epinephrine to local anesthetics and/or opioids was common practice to enhance and prolong analgesia, to decrease maternal vascular uptake and placental transfer and to identify intravascular misplacement of an epidural catheter (1,10,11). Even small concentrations of epinephrine (e.g., 1:800,000–1:1,000,000) have been reported as being successful and enabled the use of small concentrations of local anesthetics (1,12,13). In the present study, the hourly drug consumption but not the total drug consumption was significantly larger in the LS group. This may be explained by the fact that for the calculation of the hourly drug consumption, all parturients were included for analysis up to the moment the decision was made to administer rescue medication or perform a cesarean delivery. These parturients however were not considered for total drug consumption.
There are two possible mechanisms for the enhanced and prolonged analgesic effects observed with the addition of epinephrine. First, epinephrine decreases the dural blood flow, which is the primary mechanism of clearance of epidural drugs (3,6). Thus, epinephrine slows the vascular uptake of drugs from the epidural space, and as a consequence more drug may be able to diffuse into the central nervous system (3). Second, there may be a direct mechanism, as epinephrine injected alone in the lumbar epidural space has been shown to cause segmental analgesia (14). Epinephrine is absorbed in the cerebrospinal fluid and acts as a 2-receptor agonist in the dorsal horn (15). Levobupivacaine intrinsically produces more vasoconstriction than bupivacaine when injected in human skin (7). The enhanced analgesic effect of epinephrine could be less important when the local anesthetic itself has vasoconstrictor properties. However, the effect of levobupivacaine on other vascular beds (e.g., in the epidural space) are not known. Only one clinical study has evaluated the addition of epinephrine to levobupivacaine. During epidural anesthesia for lumbar spine surgery Kopacz et al. (16) found no statistical difference in onset, extent, and duration of sensory and motor blockade between plain 0.5% levobupivacaine, 0.5% levobupivacaine with 1:400,000 epinephrine, and 0.5% levobupivacaine with 1:200,000 epinephrine although intraoperative block quality was better and peak plasma concentrations of levobupivacaine tended to be smaller in those patients treated with epinephrine. There was no difference in peak plasma concentrations between 1:400,000 and 1:200,000 epinephrine. However, the large concentrations of levobupivacaine used in that study possibly obscured the effects of epinephrine.
Potential adverse effects of the addition of epinephrine are decreased uterine blood flow and contractility, prolongation of labor and an increased incidence of motor block, hypotension, pruritus, and nausea/vomiting. In most studies, these adverse side effects depend on the concentration of epinephrine and are apparent in concentrations up to 1:300,000 (2,4,5,17). For this reason only one small concentration (1:800,000) of epinephrine was examined in our study.
Most studies adding epinephrine to local anesthetics during epidural labor analgesia did not find a difference in Apgar scores or neonatal neurologic and adaptive capacity scores (4,5,10,18–20). Several factors could account for the lower Apgar scores in our LSE group: differences in hemodynamics, differences in use of oxytocin, and more motor block with prolongation of the second stage of labor resulting from decreased maternal expulsive strength with a possible resultant increase in the incidence of instrumental deliveries (2,17). In this study we did not find a difference in maternal arterial blood pressure, maternal and fetal heart rate or the use of ephedrine, nor in the use of oxytocin between the two groups. The rate in instrumental or cesarean delivery was also similar. Although in our study only a trend was present, several other studies have found more motor block in those receiving epinephrine, although this finding has not always been statistically significant (2,19,20). There was also a trend to prolongation of the second stage of labor in the LSE group. Okutomi et al. (5) found that the pH in the umbilical artery at the time of delivery was decreased possibly as the result of prolongation of the second stage of labor in the epinephrine-containing group. Apgar scores were comparable to the group not treated with epinephrine in that study.
The effect of the addition of epinephrine to epidural opioids on the incidence of pruritus is controversial. Some studies showed an increase in the incidence of pruritus (12,21), whereas others found no effect (22) or even a decrease (23). The literature is also controversial about the effects of epinephrine on the incidence of nausea and vomiting (22,24). In this study we were unable to detect differences in the incidences of pruritus, nausea and vomiting.
In conclusion, this study demonstrates that the addition of a small dose of epinephrine to an infusion of levobupivacaine plus sufentanil intensifies the analgesic effects during epidural labor analgesia. However, further study is required to evaluate its effect on motor blockade and neonatal outcome.
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Footnotes
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Accepted for publication February 27, 2006.
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Abstract
Introduction
