We thank Dr. Goddon for his interest in our recent study published in Anesthesiology1 about the comparison of different propofol formulations during induction of general anesthesia.
First, the aim of our study was not to perform a pharmacokinetic study. Our primary outcome was the required dose of propofol with or without lidocaine to achieve induction of general anesthesia. Induction was defined using bispectal index that indirectly measured the cortical effect of propofol infusion. A secondary outcome was calculated and measured propofol and lidocaine plasma concentrations as indicated in the article. This was performed only in Foch Hospital and not in other centers (for logistic reasons). No stratification was planned in the randomization and this explained an imbalance between the six groups. Our text was extremely cautious: “These results should be guardedly analyzed for several reasons: assays were done on a limited number of patients, blood samples were never taken during a steady-state period because induction is per se an unstable period and because closed-loop propofol administration consisted in several consecutive boluses at short intervals, arterio-venous difference is probably higher during such a period than during a maintenance period, […]”. A cross-over study, suggested by Goddon, cannot be considered in patients in comparison to healthy volunteers. This inevitably induces intervariability difference but represents real life.
The second point underlined by Goddon is the question of data handling when patients did not reach induction at 360 s. We have arbitrarily limited the x-axis of figure 2 (duration of anesthetic induction) to 360 s, but no data were retrieved in the analysis.
The third point is artifacts. Bispectal index has numerous possible artifacts; they were well described by Dahaba.2 Our inclusion criteria considered some of them.1 In the Materials and Method section, we allowed the possibility to “gently” ventilate patients in case of significant drop in oxygen saturation (Spo2 <92%) during induction. This rescue maneuver could modify bispectal index, if painful, but we did not record the number of such interventions.
Finally, we agree with Dr. Goddon: pain and time required for induction cannot be separated. Our article reported the differences for these parameters between formulations of propofol (long-chain triglycerides versus mixture of long- and medium-chain triglycerides) and between formulations mixed with either saline solution or lidocaine 1%.
As a conclusion, our method is probably not perfect but allows a standardization of anesthesia limiting human bias. We also want to draw anesthesiologists’ attention to the fact that there are extremely different formulations for propofol from one country to another and sometimes in the same country.*
Competing Interests
The authors declare no competing interests.
Available at: http://www.drugs.com/international/propofol.html. Accessed June 19, 2014.