JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Owen, M. D. Articles by D’Angelo, R. Search for Related Content PubMed PubMed Citation Articles by Owen, M. D. Articles by D’Angelo, R. Related Collections Regional Anesthesia Obstetrics

---

OBSTETRIC ANESTHESIA

Ropivacaine 0.075% and Bupivacaine 0.075% with Fentanyl 2 µg/mL are Equivalent for Labor Epidural Analgesia

Department of Anesthesiology, Section of Obstetric Anesthesia, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Address correspondence and reprint requests to Dr. Owen, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1009. Address e-mail to mowen{at}wfubmc.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Fifty percent effective dose estimates for ropivacaine and bupivacaine suggest that ropivacaine is 40% less potent than bupivacaine to initiate labor analgesia. At clinically used concentrations, however, the drugs seem indistinguishable for initiating and maintaining labor analgesia. We designed this study to evaluate a concentration near the reported 50% effective dose values for ropivacaine and bupivacaine in an attempt to detect differences between the drugs during routine clinical use. Fifty-nine nulliparous women in labor were randomized to receive 0.075% ropivacaine or bupivacaine, each with fentanyl 2 µg/mL. After epidural placement and the administration of a lidocaine/epinephrine test dose, 20 mL of study solution was administered and a patient-controlled epidural infusion was initiated with the following settings: 6 mL/h basal rate, 5 mL bolus, 10 min lockout, and 30 mL/h limit. Breakthrough pain was treated with 10-mL boluses of study solution. By using a study design to detect a 40% difference in hourly drug use between groups, we found no statistically significant differences in the amount of local anesthetic used, verbal pain scores, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction. We conclude that 0.075% ropivacaine and bupivacaine, with fentanyl, are equally effective for labor analgesia using the patient-controlled epidural analgesia technique.

IMPLICATIONS: At small concentrations, ropivacaine and bupivacaine when combined with fentanyl are equally effective for labor analgesia. Patients self-administered similar volumes of 0.075% ropivacaine or bupivacaine solutions containing fentanyl (2 µg/mL) suggesting that at this concentration, and with the addition of fentanyl, ropivacaine and bupivacaine can be used interchangeably.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Since the release of ropivacaine in 1996, there have been conflicting comparisons of ropivacaine and bupivacaine for labor analgesia (1–4). Studies using the up-down sequential allocation design to estimate 50% effective dose (ED₅₀) suggest that ropivacaine is 40% less potent than bupivacaine for initiating labor analgesia (1,2). In contrast, clinical studies comparing equal concentrations of ropivacaine and bupivacaine for the initiation and maintenance of labor analgesia have found the drugs to be indistinguishable (3–5). This discrepancy has created confusion; if ropivacaine is less potent than bupivacaine, larger volumes or larger concentrations of ropivacaine should be required to produce analgesia.

Clinical studies, however, may potentially mask potency differences because local anesthetic concentrations (0.125%–0.25%) are used that correspond to the upper end of a dose-response curve (approximately ED₉₅). The present study was designed to compare 0.075% ropivacaine and bupivacaine solutions containing fentanyl 2 µg/mL for labor analgesia by patient-controlled epidural infusion. By using a local anesthetic concentration near the reported ED₅₀ for ropivacaine and bupivacaine (1,2), we hypothesized that differences in potency should become apparent during labor based on the amount of each solution required to produce analgesia.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
After IRB approval and informed consent, nulliparous ASA physical status I or II women with term, singleton pregnancies were enrolled in the study. Each participant was in active labor with cervical dilation 3–6 cm and requesting epidural analgesia. Patients were excluded for weight >115 kg, age <18 yr, IV analgesic administration within 1 h of epidural request, allergy to study medication, or inability to understand English.

Once enrolled in the study, a multiorifice catheter (B. Braun Medical, Bethlehem, PA) was inserted 4–6 cm into the epidural space (L2-3 or L3-4) by using a standard approach. Three milliliters of lidocaine (1.5%) with 15 µg of epinephrine was administered through the epidural catheter as a combined subarachnoid and IV test dose. Once a negative test dose was established, 20 mL of either 0.075% ropivacaine with fentanyl 2 µg/mL or 0.075% bupivacaine with fentanyl 2 µg/mL was administered in 5-mL aliquots. Patient randomization was determined by a computer-generated list and investigators and patients were blinded to the solution type. Patient-controlled infusion devices (APMII; Abbott Laboratories, Chicago, IL) were programmed to deliver a basal infusion of 6 mL/h with a 5-mL bolus dose available every 10 min with an hourly limit of 30 mL. For inadequate analgesia during labor, anesthesia personnel administered a 10-mL supplemental dose of study solution in 5-mL increments. Patients were excluded from data analysis if they had a positive test dose, persistent inadequate analgesia (requiring more than 2 sequential supplemental doses), or delivery within 2 h of epidural catheter insertion.

A verbal pain score (VPS) was obtained by using a numeric rating scale (0 = no pain, 10 = worst pain imaginable). Pain was assessed before epidural placement and at 15, 30, and 60 min after study drug administration, then every 2 h until delivery or decision for cesarean delivery. Sensory levels to pinprick and degree of motor blockade were determined at the same time intervals. Motor block was measured with a 0–3 scale (grade 0 = can raise extended leg off bed, grade 1 = can bend knees, grade 2 = can bend ankles, grade 3 = unable to bend knees or ankles). Cumulative study solution volumes, patient-controlled epidural analgesia (PCEA) demands, and delivered demand doses were recorded at complete cervical dilation and at delivery (or at the time of decision for cesarean delivery). For incomplete perineal analgesia at delivery, patients received 10–15 mL of 2% or 3% 2-chloroprocaine. If patients required 2-chloroprocaine, this was noted but the volumes administered were not included in the totals for volume of study solution administered. Patient satisfaction was assessed after delivery as excellent, good, fair, or poor.

Monitoring included noninvasive maternal blood pressure, tocodynamometry, and continuous fetal heart rate throughout labor. Hypotension was defined as systolic blood pressure <100 mm Hg and was treated with left uterine displacement, IV fluid, or ephedrine. Fetal bradycardia (<120 bpm) was treated with left uterine displacement, maternal oxygen (10 L/min face mask), IV fluid, or ephedrine, as indicated.

Statistical analyses were performed by using Sigmastat (SPSS Inc., Chicago, IL) or SAS (Statistical Analysis System, Inc., Cary, NC). Statistical analysis included Student’s t-tests, ², and Wilcoxon’s ranked sum test as appropriate. P < 0.05 was considered significant. Sample size (25 patients per group) was estimated by using power analysis to detect a 6-mL difference in hourly drug use between groups (assuming patients administered bupivacaine/fentanyl would require 15 mL/h local anesthetic solution) and with the following additional assumptions: SD = 6.0, power = 0.90, = 0.05.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Fifty-nine patients were enrolled, and 50 completed the study. Nine patients were eliminated from analysis for the following reasons: inadequate analgesia (1 patient in the Ropivacaine group, 2 patients in the Bupivacaine group), delivery <2 h (1 patient in each group), and protocol deviation (2 patients in each group). Of the 50 patients completing the study, 25 received bupivacaine and 25 received ropivacaine. The demographic and labor and delivery characteristics of the patients were similar in each group (Table 1).

The incidence of hypotension and nausea did not differ between groups (Table 3). Ten patients in the Ropivacaine group (40%) developed hypotension and 7 (28%) received ephedrine. In contrast, 5 patients in the Bupivacaine group (20%) developed hypotension and 4 (16%) received ephedrine. (One additional patient in each group was administered ephedrine for fetal bradycardia in the absence of hypotension.) A similar dose of ephedrine was administered to each patient and all patients responded to treatment. Apgar scores were similar between groups at 1 and 5 min. Three patients in each group had infants with 1-min Apgar scores below 7. By 5 min, all Apgar scores were above 7, except for 1 infant with an Apgar of 6 in the Bupivacaine group who required intubation after a difficult labor (maternal fever and decreased fetal heart rate variability).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Consistent with previous reports using 0.125% solutions with and without fentanyl (3,4), patients in the present study self-administered similar volumes of 0.075% ropivacaine and 0.075% bupivacaine containing fentanyl 2 µg/mL to maintain labor analgesia. By using a study design to detect a 40% difference in drug use between groups, there were no statistically significant differences in the amount of local anesthetic used, pain scores, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction between groups while using a PCEA method for labor analgesia. In fact, the amounts of local anesthetic solutions used over the course of labor were nearly identical. Likewise, most clinical studies have found epidural ropivacaine and bupivacaine, with and without opioids, to be similar when compared at equal concentrations ranging from 0.125% to 0.25% for the maintenance of labor analgesia (3–9).

Two studies estimating ED₅₀, however, suggest that ropivacaine is 40% less potent than bupivacaine for initiating labor analgesia, and that this difference may account for the decreased toxicity and motor block when equal drug concentrations are compared (1,2). If this is the case, then at equally potent doses, ropivacaine may have similar toxicity and motor block to bupivacaine. If ropivacaine is less potent than bupivacaine for the maintenance of labor analgesia, then a larger concentration or a larger volume of ropivacaine should be required to produce a similar degree of labor analgesia assuming parallel dose-response curves for ropivacaine and bupivacaine. Two previous studies at the authors’ institution (3,4) using the PCEA technique compared 0.125% ropivacaine with 0.125% bupivacaine, with and without fentanyl, and found no significant differences in the dose of local anesthetic required to produce analgesia. The 0.125% concentration is at the upper end of the dose-response curve and may potentially mask potency differences between drugs. The present study was designed in an attempt to circumvent this problem by using a local anesthetic concentration (0.075%) nearer the estimated ED₅₀ value (1,2). We found, however, no differences in the volume of solution administered by patients for labor analgesia, verbal pain assessments, or patient satisfaction between 0.075% ropivacaine and bupivacaine containing fentanyl 2 µg/mL. In addition to the present study, three others (10–12) have administered relatively dilute local anesthetic solutions (0.0625%, 0.08%, and 0.1%) with opioids, using the PCEA method. Although the PCEA settings varied, the results were similar to this study. No differences were found between groups (620 patients) in the volume of local anesthetic required to produce labor analgesia and as measured by pain scores.

In contrast to PCEA studies, several studies (13,14) have compared "equianalgesic" concentrations of bupivacaine and ropivacaine based on the 0.6 relative potency difference reported in the minimum local analgesic concentration (MLAC) studies (1,2). Mandell et al. (13) administered 0.1% ropivacaine and 0.06% bupivacaine with fentanyl (2 µg/mL) for maintenance analgesia in laboring women and found lower visual analog pain scores in patients administered ropivacaine. In another study, Celleno et al. (14) administered a 20-mL bolus of 0.1% ropivacaine and 0.06% bupivacaine with sufentanil 10 µg and found significantly longer analgesia with ropivacaine (119 min versus 89 min). Two additional studies compared local anesthetics using a 20% (rather than 40%) concentration difference (5,15). Gautier et al. (5) reported significantly less analgesia (and more motor block) from 0.1% bupivacaine with 7.5 µg of sufentanil than from 0.125% ropivacaine with 7.5 µg of sufentanil when administered by intermittent bolus. Similarly, patients administered a continuous infusion (10 mL/h) of 0.125% ropivacaine with 2 µg/mL fentanyl had better analgesia than did patients administered 0.1% bupivacaine with 2 µg/mL fentanyl (15). These studies infer that relatively more ropivacaine than bupivacaine was administered (5,13–15) and had equal concentrations been used, labor analgesia may have been similar. An alternative explanation for the observed differences in the duration and quality of analgesia could be that ropivacaine is more vasoactive than bupivacaine and that a larger concentration of ropivacaine was administered.

It is important to understand why findings from clinical studies differ from those designed to estimate the MLAC. One reason may be the different methodologies and outcome expectations used by the study types. By definition, in the MLAC studies, 50% of patients will experience success by the stated criteria, and 50% failure when administered a local anesthetic solution to initiate labor analgesia. By this method, ED₅₀ is estimated and relative potency can be determined by the left and right positions of a concentration-effect curve along the concentration, or x axis. In contrast, clinical studies are designed to produce analgesia in the majority of patients for the duration of labor and assess drug efficacy. Analgesic efficacy is the degree of a drug’s response toward a maximal effect, corresponding to the height of the concentration-effect curve, or the plateau along the y axis. Clinical studies suggest that ropivacaine and bupivacaine must have different dose-response curves to account for a 40% potency difference at the ED₅₀. In addition, several other limitations of clinical studies make comparisons with MLAC studies difficult. First, in clinical studies, opioids are frequently added to local anesthetic solutions. Opioids reduce local anesthetic requirements by 19% to 31% (16,17) and combination drug use obscures comparisons with studies using plain local anesthetic solutions. Second, it is uncertain whether the PCEA technique can be used to qualitatively compare different local anesthetics by the volume of solution used. Taken together, it may be inaccurate to make statements about drug potency based on the results of clinical studies.

Limitations of MLAC studies, however, include difficulty in applying results to the clinical setting. Although it is useful to compare relative drug potency at the ED₅₀, it remains uncertain whether MLAC studies can be used to predict the ED₉₅, a more clinically important value. In one MLAC study (2), for example, it was estimated that a concentration of 0.22% ropivacaine (44 mg) would be required for 90% of labor patients to achieve a VAS <10 mm, 30 minutes after a 20-mL bolus. Based on our previous (4) and present clinical studies, we contend that the dose of ropivacaine required to produce labor analgesia in 90% of patients (approximately ED₉₅) is closer to 20 mg. In our study design, however, the use of fentanyl 2 µg/mL, the addition of a test dose, and variations in patient populations could have accounted for the difference between the calculated and clinical dose requirements.

Frequently, studies are conducted without full knowledge of drug potency or the dose-response curves. Ideally, a full dose-response curve with a maximal effect and a known slope is used to derive an ED₅₀ value. This method is used in the laboratory, but it is time and resource consuming and difficult to apply in the clinical setting. Studies using an up-down sequential allocation design are efficient, provide useful information about relative potency differences at the ED₅₀, and have appropriately raised questions regarding the reduced motor block and toxicity reported with ropivacaine. If ropivacaine is less potent than bupivacaine, the potential benefits regarding toxicity and motor block will remain controversial until the relative therapeutic ratios have been established.

One limitation of this study may have been the use of a lidocaine/epinephrine test dose after epidural catheter placement. In a recent article by Cohen et al. (18), a standard 3-mL-1.5% lidocaine with 15-µg epinephrine test dose significantly inhibited motor function (ambulation) when administered before 12 mL of 0.125% bupivacaine/sufentanil. Motor function was not affected, however, when the same test dose was given before 12 mL of 0.0625% bupivacaine/sufentanil solution. Test dose use did not significantly alter pain scores but there was a trend toward lower pain scores when a test dose was used (18). In this study, the local anesthetic concentration was 0.075%; therefore, it is possible that administering a test dose could have altered sensory and motor block. By using the same test dose in each group, however, one would expect that the magnitude of change, if any, would have been similar between groups.

In addition, there was a frequent incidence of instrumental delivery in the Ropivacaine group, although this was not statistically significant with the small sample size used. We made no attempt to control for instrumental deliveries, and the use of low or outlet forceps at our institution varies considerably with obstetrical practice patterns. Patients receiving ropivacaine were somewhat more likely to require a perineal dose (not statistically significant) during the second stage of labor and perhaps this contributed to the trend toward a more frequent instrumental delivery rate. We observed a similar trend in our previous study (4); supplemental local anesthetic was required more frequently at delivery in the 0.125% Ropivacaine/Fentanyl group compared with the 0.125% Bupivacaine/Fentanyl group, but the instrumental delivery rates were identical (16%).

In summary, it seems that over a wide dose range (0.0625%–0.125%) with and without opioids, patient-controlled epidural infusions of equal concentrations of ropivacaine and bupivacaine produce similar labor analgesia and can be used interchangeably. In the present study, 0.075% ropivacaine and 0.075% bupivacaine, containing fentanyl 2 µg/mL, produced equivalent analgesia for labor. There were no statistically significant differences in the amount of local anesthetic used, pain scores, sensory levels, motor blockade, labor duration, mode of delivery, side effects, or patient satisfaction between the local anesthetics using the PCEA technique.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Polley LS, Columb MO, Naughton NN, et al. Relative analgesic potencies of ropivacaine and bupivacaine for epidural analgesia in labor: implications for therapeutic indexes. Anesthesiology 1999; 90: 944–50.[ISI][Medline]
2. Capogna G, Celleno D, Fusco P, et al. Relative potencies of bupivacaine and ropivacaine for analgesia in labour. Br J Anaesth 1999; 82: 371–3.[Abstract/Free Full Text]
3. 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]
4. Meister GC, D’Angelo R, Owen M, et al. A comparison of epidural analgesia with 0.125% ropivacaine with fentanyl versus 0.125% bupivacaine with fentanyl during labor. Anesth Analg 2000; 90: 632–7.[Abstract/Free Full Text]
5. 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.[ISI][Medline]
6. Stienstra R, Jonker TA, 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.[Abstract]
7. 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.[Abstract/Free Full Text]
8. 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.[Abstract/Free Full Text]
9. McCrae AF, Jozwiak H, McClure JH. Comparison of ropivacaine and bupivacaine in extradural analgesia for the relief of pain in labour. Br J Anaesth 1995; 74: 261–5.[Abstract/Free Full Text]
10. Smiley RM, Kim-Lo SH, Goodman SR, et al. Patient-controlled epidural analgesia with 0.0625% ropivacaine versus bupivacaine with fentanyl during labor [abstract]. Anesthesiology 2000; 93: A1065.
11. Breen TW, Campbell DC, Kronberg JE, et al. The clinically relevant potencies of ropivacaine and bupivacaine: a PCEA study [abstract]. Anesthesiology 2000; 93: A1101.
12. Fischer C, Blanie P, Jaouen E, et al. Ropivacaine, 0.1%, plus sufentanil 0.5 µg/ml, versus bupivacaine 0.1%, plus sufentanil 0.5 µg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison. Anesthesiology 2000; 92: 1588–93.[ISI][Medline]
13. Mandell G, Makishima S, Ramanathan S. Is 0.1% ropivacaine equipotent to 0.06% bupivacaine? A double-blinded, randomized study [abstract]. Anesthesiology 2000;SOAP Suppl:A65.
14. Celleno D, Parpaglioni R, Capogna G, et al. Low-dose ropivacaine and bupivacaine at equianalgesic concentration for epidural analgesia during the first stage of labor. International Monitor Special Abstract Issue. Eighteenth Annual ESRA Congress 1999; 11: 40.
15. Hughes D, Hill D, Fee H. A comparison of bupivacaine-fentanyl with ropivacaine-fentanyl by epidural infusion for labor analgesia [abstract]. Anesthesiology 2000; 93: A1051.
16. Lyzak SZ, Eisenach JC, Dobson CE. Patient-controlled epidural analgesia during labor: a comparison of three solutions with a continuous infusion control. Anesthesiology 1990; 72: 44–9.[ISI][Medline]
17. Lyons G, Columb M, Hawthorne L, Dresner M. Extradural pain relief in labour: bupivacaine sparing by extradural fentanyl is dose dependent. Br J Anaesth 1997; 78: 493–7.[Abstract/Free Full Text]
18. Cohen SE, Yeh JY, Riley ET, Vogel TM. Walking with labor epidural analgesia: the impact of bupivacaine concentration and a lidocaine-epinephrine test dose. Anesthesiology 2000; 92: 387–92.[ISI][Medline]

This article has been cited by other articles:

				M. Supandji, A. T. H. Sia, and C. E. Ocampo 0.2% ropivacaine and levobupivacaine provide equally effective epidural labour analgesia: [La ropivacaine et la levobupivacaine a 0,2 % par voie epidurale ont un effet analgesique similaire pendant le travail] Can J Anesth, November 1, 2004; 51(9): 918 - 922. [Abstract] [Full Text] [PDF]

				B. B. Lee, W. D. Ngan Kee, F. F. Ng, T. K. Lau, and E. L. Y. Wong Epidural Infusions of Ropivacaine and Bupivacaine for Labor Analgesia: A Randomized, Double-Blind Study of Obstetric Outcome Anesth. Analg., April 1, 2004; 98(4): 1145 - 1152. [Abstract] [Full Text] [PDF]

				M. Senard, A. Kaba, M. J. Jacquemin, L. M. Maquoi, M.-P. N. Geortay, P. D. Honore, M. L. Lamy, and J. L. Joris Epidural Levobupivacaine 0.1% or Ropivacaine 0.1% Combined with Morphine Provides Comparable Analgesia After Abdominal Surgery Anesth. Analg., February 1, 2004; 98(2): 389 - 394. [Abstract] [Full Text] [PDF]

				Y. Lim, C. E. Ocampo, and A. T. Sia A Comparison of Duration of Analgesia of Intrathecal 2.5 mg of Bupivacaine, Ropivacaine, and Levobupivacaine in Combined Spinal Epidural Analgesia for Patients in Labor Anesth. Analg., January 1, 2004; 98(1): 235 - 239. [Abstract] [Full Text] [PDF]

				J.-M. Bernard, D. Le Roux, and J. Frouin Ropivacaine and Fentanyl Concentrations in Patient-Controlled Epidural Analgesia During Labor: A Volume-Range Study Anesth. Analg., December 1, 2003; 97(6): 1800 - 1807. [Abstract] [Full Text] [PDF]

				L. S. Polley and M. O. Columb Ropivacaine and Bupivacaine: Concentrating on Dosing! Anesth. Analg., May 1, 2003; 96(5): 1251 - 1253. [Full Text] [PDF]

				S. H. Halpern and V. Walsh Epidural Ropivacaine Versus Bupivacaine for Labor: A Meta-Analysis Anesth. Analg., May 1, 2003; 96(5): 1473 - 1479. [Abstract] [Full Text] [PDF]

				E. Boselli, R. Debon, F. Duflo, B. Bryssine, B. Allaouchiche, and D. Chassard Ropivacaine 0.15% Plus Sufentanil 0.5 {micro}g/mL and Ropivacaine 0.10% Plus Sufentanil 0.5 {micro}g/mL Are Equivalent for Patient-Controlled Epidural Analgesia During Labor Anesth. Analg., April 1, 2003; 96(4): 1173 - 1177. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Owen, M. D. Articles by D’Angelo, R. Search for Related Content PubMed PubMed Citation Articles by Owen, M. D. Articles by D’Angelo, R. Related Collections Regional Anesthesia Obstetrics

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999