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LETTERS TO THE EDITOR

Ropivacaine and Bupivacaine with Fentanyl for Labor Epidural Anesthesia

Department of Anaesthesia Leeds General Infirmary Leeds, UK

To the Editor:

Meister et al. (1) compared epidural analgesia with 0.125% ropivacaine/fentanyl versus 0.125% bupivacaine/fentanyl during obstetric labor. The local anesthetics used were of equal concentration but were not equianalgesic. Minimum local analgesic concentration studies have demonstrated that ropivacaine has only 0.6 the potency of bupivacaine (2,3), and therefore, equiconcentration but not equipotent drugs have been used. The concentrations used, 0.125% local anesthetic, are both above their calculated 95% effective doses, and therefore, both would be expected to provide effective analgesia, as demonstrated in the study.

That significantly less motor block was seen in the ropivacaine/fentanyl group is not surprising in view the lower potency of ropivacaine. The authors state that ropivacaine cannot be less potent than bupivacaine as less supplemental analgesia was needed in the ropivacaine group. This simply reflects the longer half-life of ropivacaine compared with bupivacaine, a result of its S-enantiomer form and its greater vasoconstrictor action. The conclusion that the drugs appear to be equipotent at clinically used concentrations only reflects the higher than 95% effective dose concentrations being used.

References

1. 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]
2. 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.[Web of Science][Medline]
3. 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]

Response

Section on Obstetrical Anesthesia Department of Anesthesiology Wake Forest University School of Medicine Winston-Salem, NC 27103

In Response:

We read with interest Drs. Pinder’s and Dresner’s comments and appreciate the opportunity to respond. Their comments only reinforce the "concerns" we have with respect to the relative potencies of bupivacaine and ropivacaine estimated with the up-down study design (1,2). Although we in no way dispute these findings, differences in potency at low concentrations in a study setting may not necessarily apply to the higher concentrations typically used in clinical practice. In addition, up-down study findings can not substitute for traditional dose-response studies, which along with clinical studies, guide clinical practice. Yet, as the letter by Drs. Pinder and Dresner indicates, practicing anesthesiologists attempt to apply up-down study findings to clinical practice. The major contribution of these studies is that the issue of relative potency is now revealed. Clinical studies must now be designed to test for differences in potency between bupivacaine and ropivacaine by using clinically relevant drug concentrations. In fact, three separate abstracts presented at the Society for Obstetric Anesthesia and Perinatology 2000 Annual Meeting specifically addressed this issue and concluded that, even at ultra small-dose concentrations, there are no clinical differences in potency between epidural bupivacaine and ropivacaine (3–5).

Now let us specifically address in detail some of the issues raised by Drs. Pinder and Dresner. Although up-down study findings suggest ropivacaine is 40% less potent than bupivacaine (1,2), clinical studies comparing the two local anesthetics suggest they are equipotent in terms of clinically meaningful endpoints such as drug use, pain scores, and side effects (3,4,6). In contrast, the only study that compares "equipotent concentrations as indicated by up-down studies," administered ropivacaine 0.1% and bupivacaine 0.06% and reported lower visual analog scale (VAS) pain scores with ropivacaine, indicating relatively more ropivacaine was administered (5).

A 95% effective dose (ED₉₅) cannot be reliably estimated from an up-down study. By design, the strength of an up-down study is that all data points concentrate around the 50% effective dose (ED₅₀) so that the ED₅₀ can be estimated with relatively few patients. However, this strength is also the primary weakness, no other points along the dose-response curve can be estimated with any degree of statistical certainty. Thus, up-down studies cannot substitute for traditional dose-response studies and because traditional dose-response curves for ropivacaine and bupivacaine are lacking, the ED₉₅ of each remains unknown. Our studies were designed to mimic clinical practice (6,7). We administered 0.125% concentrations of bupivacaine and ropivacaine because this concentration is commonly used in clinical practice and produces analgesia in most patients (not only 50% of patients) without producing excessive side effects. Because physicians typically administer doses of drugs closer to the ED₉₅ rather than the ED₅₀, studies that administer higher concentrations answer the anesthesiologist’s bottom line: how do I produce labor analgesia in my patient?

Although we found statistically less motor block in patients administered ropivacaine in this particular study (7), 74% of all studies and 82% of obstetric studies that compare motor block produced from bupivacaine and ropivacaine report no difference in motor block between the two local anesthetics (8). While not attempting to explain this discrepancy in this reply, it remains to be determined if this slight potential difference in motor block (all patients but one in our study experienced either no motor block or minimal motor block) affects outcome.

In three separate studies, we compared epidural bupivacaine and ropivacaine in laboring patients (3,6,7). In each study, patients self-administered similar amounts of each local anesthetic, and we concluded the drugs are clinically indistinguishable. Drs. Pinder and Dresner suggest the longer half-life of ropivacaine, vasoconstrictor actions of ropivacaine, and/or the higher-than-ED₉₅ concentrations used may have confounded our findings. Whatever the reason, the fact remains that patients require similar doses of each local anesthetic to produce similar degrees of labor analgesia. Our clinical studies mimic clinical practice, and our findings suggest that similar concentrations of ropivacaine or bupivacaine should be administered in laboring patients, regardless of the up-down ED₅₀ estimations of potency.

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.
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.
3. Smith T, Thomas JA, Owen MD, et al. 0.075% epidural ropivacaine and bupivacaine are clinically indistinguishable for labor analgesia. Anesthesiology SOAP Supplement 2000; A24.
4. Kim-lo SH, Jackson M, Goodman S, et al. PCEA comparison of ropivacaine versus bupivacaine 0.0625%: no difference. Anesthesiology SOAP Supplement 2000;:A61.
5. Mandell G, Makishima S, Ramamathan S. Is 0.1% ropivacaine equipotent to 0.06% bupivacaine? A double-blinded randomized study. Anesthesiology SOAP Supplement 2000;:A65.
6. 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]
7. 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.
8. Medline search through the National Library of Medicine. PubMed Project, National Institutes of Health.

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