In Reply:—

We thank Dr. Overdyk for his comments, which argue that repeated doses of propofol do produce tolerance in children. However, the results of previous work in this field, which were mostly based on clinical criteria alone, are inconclusive.1,2In our study,3we used the same conventional dose of propofol in all cases and in all the procedures, namely, a fixed dose of 5-mg/kg bolus followed by a continuous infusion of 150 μg · kg−1· min−1. The option given to the anesthesiologist in charge to administer extra doses of propofol when necessary was rarely used, and the few extra doses that were eventually given were evenly distributed among the 6 weeks of treatment. We did not claim that such a predetermined regimen will result in a “fixed” propofol concentration at the effect site. We did, however, expect that if tolerance had developed during repeated exposures, it would have expressed itself by either a change in Bispectral Index or clinical criteria. We agree with Dr. Overdyk’s suggestion that the use of target-controlled infusion of propofol may have theoretical advantages in conducting such study, although the use of target-controlled infusion in children has not yet been validated. Although it is true that the Bispectral Index nadirs occurring immediately after the induction of anesthesia were low, they increased rapidly to values of 40–60, as shown in figure 2 in our article. Our results clearly show that in 15 patients, each undergoing a mean of 24 treatments, both the Bispectral Index profiles and all of the clinical criteria did not change and that there was no need to increase the initial conventional propofol dosage.

* Tel Aviv University, Tel Hashomer, Israel.


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