Agitation After Desflurane and Dixon and Massey Up-and-Down Method

To the Editor:

We have read with interest the recent articles by Cohen et al. ^(1,2) on emergence agitation after general anesthesia in children. In the first of the studies, the authors used the Dixon and Massey ⁽³⁾ up-and-down method to determine the ED50 of fentanyl to reduce emergence agitation after desflurane in children who underwent otorhinolaryngologic surgery ⁽¹⁾. We are a bit worried with regard to the use of this methodology in this study design. The Dixon and Massey up-and-down method has been thought to account for dichotomous variables or outcomes (i.e., agitation or no agitation), one of which should occur 100% of the time that the patient is not undergoing the appropriate intervention (i.e., adequate dose of fentanyl) ⁽³⁾. In the aforementioned study, however, the authors used the classic up-and-down method to define the ED50 of fentanyl to reduce the incidence of an outcome such as agitation that they expect to occur in no more than 80% of the cases and eventually in only half the number of patients ⁽¹⁾. Thus, in the best scenario, at each dose and just by chance, 20% (but even up to 50%) of the cases will not present agitation resulting in a reduction of the dose for the next case, finally leading to an underestimation of the ED50. Although in a subsequent study the ED50 of fentanyl so determined seems to work ⁽²⁾, we think that the Dixon and Massey up-and-down method was incorrectly used.

Hernán R. Muñoz, MD

Mauricio E. Ibacache, MD