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From the Department of Anesthesia O & G, Kandang Kerbau Hospital, Singapore.
Address correspondence to: Dr. Mia Supandji, Department of Anesthesia O & G, KK Women and Children Hospital, 100 Bukit Timah Road, Singapore. E-mail: athsia{at}kkh.com.sg
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Abstract |
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Methods: Forty healthy nulliparous parturients with cervical dilatation of 3 to 5 cm and at least one contraction every two or three minutes were recruited. Patients were randomly assigned to receive either 10 mL of 0.2% ropivacaine or 10 mL of 0.2% levobupivacaine. Preblock visual analogue scale (VAS) score (0–100) and VAS score after five, ten, 15, 20, 25 and 30 min from time0 and VAS at time of request for additional analgesia (timeend) were recorded.
During the first 30 min after the completion of epidural injection, the systolic blood pressure, highest sensory level to cold and the maximum degree of motor block based on a 0 to 3 modified Bromage scale were collected every five minutes. The duration of analgesia was defined as the time from time0 to timeend.
Results: There was no difference in the duration of analgesia between the two groups; similarly, there was no significant difference found in the area under the curve (AUC) time15-time0 and AUC time30-time0 for VAS. The highest sensory block to cold and the degree of motor block were also indistinguishable between the two groups. No difference in the serial systolic blood pressures was found.
Conclusion: Ten millilitres of either 0.2% ropivacaine or levobupivacaine can be used to induce epidural labour analgesia effectively without a difference in the duration of pain relief.
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Introduction |
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Even though the potency of ropivacaine was originally purported to be similar to bupivacaine for labour epidural analgesia5,6 recent evidence suggests that ropivacaine could be less potent than bupivacaine.7,8 The R-isomer of bupivacaine has also been found to be more potent in effecting sodium and potassium channel blockade in vitro than the S-isomer,9 albeit the potency of levobupivacaine has been reported to be comparable with racemic bupivacaine in labour epidural analgesia.10
Our study was designed primarily to compare the duration of epidural analgesia induced by levobupivacaine and ropivacaine at clinically relevant doses.
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Methods |
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Before the institution of epidural analgesia, a pre-block pain score based on the 0 to 100 visual analogue scale (VAS; 0 = no pain and 100 = worst pain imaginable) was obtained. Systolic blood pressure (SBP), measured non-invasively from the right brachial artery (Dinamap, Critikon, Tampa, FL, USA), was also recorded while the parturient was in the supine position with a 30° wedge under the right hip to effect a left lateral tilt. While infusing 500 mL iv of Ringer’s lactate solution, the parturients were positioned in the left lateral or sitting position. The epidural space at the L3–4 intervertebral space was then accessed with a 18-gauge Tuohy needle (Perifix, B. Braun, Melsungen, Germany) by using the loss of resistance to saline technique 
4 mL, under aseptic conditions by the principal author (M.S.). A multiorifice catheter was then advanced and 3 to 4 cm were left in the epidural space. If blood/fluid was detected on aspirating the epidural catheter with a 2-mL syringe, the catheter would be replaced in an adjacent (L2–3 or 4–5) intervertebral space.
After placement of the epidural catheter, subjects were placed in the supine position with a 30° wedge under the right hip. They were then assigned by using sealed opaque envelopes to receive either 10 mL of either ropivacaine hydrochloride 0.2% (Naropin, AstraZeneca, MöIndal, Sweden; group R) or 10 mL of levobupivacaine hydrochloride 0.2% (Chirocaine, Abbott, Queenborough, Kent, UK; group L). Normal saline was used to dilute the drugs to obtain the desired concentrations. For the purpose of this study no test dose was administered. Neither the principal investigator (M.S.) nor the parturients were aware of the contents of the syringes. The test solutions were injected in one minute through the epidural catheter in two aliquots, five minutes apart. The time of completion of epidural injection was defined as time0. Parturients who had a sensory block to cold (using ice) higher than the fourth thoracic dermatome (T4), hypotension (SBP reduction of more than 20% of preblock value) or motor block (could not raise either extended leg off the bed) after the first aliquot were to be investigated for possible intrathecal/subdural placement of the catheter and excluded from the study.
VAS scores after five, ten, 15, 20, 25 and 30 min from time0 and at the time of request for additional analgesia were recorded. If the VAS score was > 30 after 15 min, an additional 5 mL of the experimental solution would be injected epidurally. In this case, the block would be labelled as ‘inadequate’ but data would be collected and analyzed as per an intention-to-treat approach. If, despite this, the VAS remained > 30 half of an hour after time0, the catheter would be labelled as ‘ineffective’ and the subject excluded from the study. In this case, the epidural catheter might be re-sited or supplemental analgesics administered, depending on the clinical situation.
During the first 30 min after the completion of epidural injection, the following data were collected:
1) SBP at five, ten, 15, 20, 25 and 30 min;
2) highest sensory level to temperature differences (loss of cold to ice) at the midline at five, ten, 15, 20, 25 and 30 min;
3) maximum degree of motor block of either lower limb based on a 0 to 3 modified Bromage scale (0 = can raise extended leg off bed, 1 = can bend knees, grade 2 = can bend ankles, grade 3 = unable to bend knees or ankles) at five, ten, 15, 20, 25 and 30 min.
The duration of analgesia was defined as the time from time0 to the time of request for additional analgesia (timeend). During this time, the subjects would be observed every 20 min for nausea and/or vomiting (0 = no, 1 = yes). At timeend, supplemental analgesia of 8 to 12 mL of the test drug would be given.
Fetal heart rate and the frequency of uterine contractions were monitored continuously by an external cardiotocogram (C.T.G.) and assessed by the attending obstetrician who was not involved in the study. New changes suggestive of an abnormal (nonreassuring) fetal heart pattern within a half hour after time0 would be noted and appropriate obstetric intervention would be effected. All preblock fetal heart tracings were confirmed to be reactive prior to the study. Maternal hypotension was defined as a decrease in SBP by more than 20% of baseline value and boluses of iv ephedrine 5 mg would be given. Nausea and vomiting would be treated with iv metoclopramide if the parturient agreed.
The maternal weight, height and SBP of the two study groups were compared by using an unpaired t test. The duration of analgesia, preblock VAS, cervical dilatation and highest sensory block were analyzed with a Mann-Whitney U test. Serial SBP were analyzed with the repeated measure analysis of variance. The onset of analgesia was computed from the area under the curve (AUC time15-time0) described by VAS vs time over the first 15 min after time0, using the trapezoid rule. Similarly, the overall pain reduction in the first 30 min postblock was obtained from the AUC time30-time0 of the VAS·time curve. The AUCs of the two groups were compared and analyzed with a Mann Whitney U test. Dichotomous data were analyzed with the Chi-square test. With 
= 0.05 and ß = 0.2, the sample size was computed to detect a difference of 30 min of analgesia between the two groups. SPSS® v. 9 (SPSS Inc., Chicago, IL, USA) was used for data entry and analyses.
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Results |
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). The mean of duration of analgesia for group L is 90.50 min (± 31.72 min) and group R is 103.30 (± 37.52 min). Similarly, there was no significant difference found in the AUC time15-time0 and AUC time30-time0 between the two groups. The highest sensory level and degree of motor block were also indistinguishable between the two groups (Table II). No parturient developed more than a grade 1 lower limb motor block.
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). No parturient developed hypotension or nausea and/or vomiting. Fetal bradycardia was not detected within a half hour of time0 in any parturient.
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Discussion |
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Recent studies have also shown, based on the up/down sequential allocation method, no statistical difference between the minimum local analgesic concentration between levobupivacaine and ropivacaine.11,12
So far, studies comparing epidural racemic bupivacaine with ropivacaine have revealed conflicting results. Studies based on up/down sequential allocation design have suggested that ropivacaine is possibly less potent than racemic bupivacaine.7,8 However, apart from estimating the 50% ‘effective dose’ (ED50), these studies do not provide adequate information regarding more clinically relevant doses, such as ED95. On the other hand, several recent studies have inferred that ropivacaine and bupivacaine are equipotent.13,14 Therefore, while the ED50 of the two drugs may vary, it is also possible that the dose-response curves overlap at higher and perhaps more clinically relevant doses.15 Consequently, in our clinical study we intended a priori to compare levobupivacaine with a similar dose of ropivacaine that had been found earlier to be effective in a majority of parturients under the same circumstances.16 Our findings support the notion that, at these doses, the clinical profiles of ropivacaine and levobupivacaine are indistinguishable.
A previous study has also shown the lack of difference in the onset and the duration of labour analgesia between epidural boluses of 0.25% ropivacaine and bupivacaine.6 In this light, the outcome of our study is not surprising. However, drawing conclusions on levobupivacaine based on earlier experience with bupivacaine remains questionable. Indeed, extrapolating the effects of racemic bupivacaine to levobupivacaine should be undertaken with caution as the S-isomer(levo) has been found to possess vasoconstrictive properties, apart from being a less potent channel blocker than its r(dextro) counterpart.9 The comparison between levobupivacaine and racemic bupivacaine is further complicated by the fact that the concentration of levobupivacaine is expressed as mg·mL–1 of base drug, whereas the concentration of bupivacaine is expressed as mg·mL–1 of hydrochloride salt. Therefore, at the same apparent concentration, levobupivacaine possesses 13% more active molecules than its racemic counterpart.17 Similarly, even though we compared the same apparent concentration of levobupivacaine and ropivacaine, i.e., 0.2%, the same volume of levobupivacaine solution would contain more active molecules than ropivacaine.
In conclusion, our study shows that 10 mL of either 0.2% ropivacaine or levobupivacaine can be used to induce epidural labour analgesia reliably, without a difference in the duration of pain relief. Apart from mild lower limb motor block in a minority of parturients, we were unable to demonstrate significant adverse effects such as hypotension, fetal bradycardia or maternal nausea/vomiting, although sample size was admittedly small. Owing to their favourable cardiotoxicity profile, levobupivacaine and ropivacaine are good substitutes of bupivacaine for the induction of epidural analgesia during labour.
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Footnotes |
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Accepted for publication February 24, 2004. Revision accepted May 14, 2004.
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References |
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2 Knudsen K, Suurkula MB, Blomberg S, Sjovall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78: 507–14.
3 Huang YF, Pryor ME, Mather LE, Veering BT. Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 1998; 86: 797–804.[Abstract]
4 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.
5 Stienstra R, Jonker TA, Bourdrez P, Kuijpers JC, van Kleef JW, Lundberg U. Ropivacaine 0.25% versus bupivacaine 0.25% for continuous epidural analgesia in labor: a double-blind comparison. Anesth Analg 1995; 80: 285–9.[Abstract]
6 Eddleston JM, Holland JJ, Griffin RP, Corbett A, Horsman EL, Reynolds F. A double-blind comparison of 0.25% ropivacaine and 0.25% bupivacaine for extradural analgesia in labour. Br J Anaesth 1996; 76: 66–71.
7 Polley LS, Columb MO, Naughton NN, Wagner DS, van de Ven CJ. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology 1999; 90: 944–50.[Medline]
8 Capogna G, Celleno D, Fusco P, Lyons G, Columb M. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999; 82: 371–3.
9 McLeod GA, Burke D. Levobupivacaine. Anaesthesia 2001; 56: 331–41.[Medline]
10 Lyons G, Columb M, Wilson RC, Johnson RV. Epidural pain relief in labour: potencies of levobupivacaine and racemic bupivacaine. Br J Anaesth 1998; 81: 899–901.
11 Polley LS, Columb MO, Naughton NN, Wagner DS, van de Ven CJ, Goralski KH. Relative analgesic potencies of levobupivacaine and ropivacaine for epidural analgesia in labor. Anesthesiology 2003; 99: 1354–8.[Medline]
12 Benhamou D, Ghosh C, Mercier FJ. A randomized sequential allocation study to determine the minimum effective analgesic concentration of levobupivacaine and ropivacaine in patients receiving epidural analgesia for labor. Anesthesiology 2003; 99: 1383–6.[Medline]
13 Owen MD, Thomas JA, Smith T, Harris LC, D’Angelo R. Ropivacaine 0.075% and bupivacaine 0.075% with fentanyl 2 µg/mL are equivalent for labor epidural analgesia. Anesth Analg 2002; 94: 179–83.
14 Owen MD, D’Angelo R, Gerancher JC, et al. 0.125% ropivacaine is similar to 0.125% bupivacaine for labor analgesia using patient controlled epidural infusion. Anesth Analg 1998; 86: 527–31.[Abstract]
15 D’Angelo R, James RL. Is ropivacaine less potent than bupivacaine? (Editorial). Anesthesiology 1999; 90: 941–3.[Medline]
16 Beilin Y, Galea M, Zahn J, Bodian CA. Epidural ropivacaine for the initiation of labor epidural analgesia: a dose finding study. Anesth Analg 1999; 88: 1340–5.
17 Schug SA. Correction factor for comparisons between levobupivacaine and racemic bupivacaine (Letter). Reg Anesth Pain Med 2001; 26: 91.[Medline]
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