Is the minimum local analgesic concentration method robust enough?

To the Editor:—We read with interest the articles by Polley et al. and Benhamou et al. in which they simultaneously published the same study in terms of objective and design performed on different continents. Minimum local analgesic concentration results, including the potency ratios, were surprisingly different from expectations. In a similar study comparing bupivacaine and ropivacaine minimum local analgesic concentrations, Polley et al. in the United States and Capogna et al. in Italy found different results although the exact same potency ratios. This makes us wonder if the current inconsistencies in results were just intercontinental differences or something else? The possible explanations we propose that were not commented in either study are as follows: 1) No real difference between the drugs. There were no statistical differences in either study, so we should accept the fact as it is. Why did this happen, having in mind all the evidence gathered so far that there is a potency rank? No clue, except for: 2) Chance, which is always a possibility. Here is our greatest concern about the method: When we study subtle differences (i.e., 15 or 20 percent), is the minimum local analgesic concentration method powerful enough to detect these differences without changing the number of subjects to be studied? As this issue is one of the strengths of the up and down sequential allocation method (to detect this clinically small difference), we might need more patients to be included in the design. We encourage the authors to deepen in the interpretation of the “negative” results. We are sure they are as surprised as we are. 3) End point: Is ED50 for pain relief in first-stage labor in the vicinity of the lower part of the dose-response curve for both drugs? Can this be the same kind of effect, but on the opposite part of the curve, when we use supramaximal doses and the potency relationship is lost? Maybe if we analyze another end point, namely motor block, a higher dosage requirement and potency differences will become more apparent. Finally, we agree with Benhamou et al. that further studies are required to verify this hypothesis.