To the Editor:
With great interest I read the study by Le Guen et al.1 on the comparison of the potency of different propofol formulations that was published in February issue of Anesthesiology. The authors compared the dose of Diprivan® (AstraZeneca, Cheshire, United Kingdom), Propoven® (Fresenius-Kabi AG, Bad Homburg, Germany), and Lipuro® (B-Braun, Melshungen AG, Germany) alone or in combination with lidocaine, which was necessary to achieve induction of general anesthesia, measured by a bispectral index (BIS)–controlled closed-loop system. I have, however, some concerns about the methodology that may undermine the clinical validity of the authors’ conclusions.
The most reliable way to compare pharmacologic potency of different drug formulations is a crossover study with healthy individuals either in a single center or with unified laboratory assessments. Otherwise, interindividual variations in pharmacodynamics might reduce validity of the findings substantially. The authors themselves criticize other studies for “ignoring high interindividual variability of the dose–effect relationship.” Yet, they chose to conduct a multicenter study and included patients ranging from American Society of Anesthesiologists I to III. The resulting interindividual variability in both BIS and propofol sensitivity are confounding factors that influence the closed-loop system. Another point of concern is the dose measurement in multiple centers, which also suffers from a very low sample size. Especially Propoven® with saline was measured only in four patients. Any results based on this sample size are prone to high statistical variability.
Concerning data handling, the authors do not report whether data from patients who had not reached induction at 360 s (which can be seen in figure 2 of the original article) were used for the analysis. Because the primary study outcome was “the dose of propofol given alone or associated with lidocaine until the moment of induction,” this information seems quite relevant.
A patient’s BIS is prone to artifacts,2,3 and those can directly influence propofol dose administered by a BIS-controlled closed-loop system. Notably, “gentle manual assistance if Spo2 decreased below 92%” as described in the methods will influence the BIS, and the authors did not state how often and in which group this measure was applied. In addition, since pain delays the time until induction, the effects of formulation potency and pain-induced induction delay cannot be separated in the analysis. In conclusion, I am not convinced that the data presented by Le Guen et al.1 demonstrate clinically relevant differences in potency between propofol formulations.
Dr. Goddon has previously received funding from Deutsche Forschungsgemeinschaft (German Research Foundation), Bonn, Germany, and Viasys Healthcare, Höchberg, Germany.
The author declares no competing interests.