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Department of Anesthesiology, Catholic University of Chile, Santiago, Chile
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.
References
Departments of Anesthesiology and Pediatrics, The George Washington University Medical Center and Staff Attending, Children’s National Medical Center, Washington, DC
In Response:
I thank Drs. Muñoz and Ibacache for their interest and comments concerning the papers by my colleagues and me on the effect of fentanyl on emergence agitation in children after anesthesia with desflurane (1,2). We agree that it is essential that the up-and-down method described by Dixon and Massey (3) be applied appropriately. Although the method was developed with the use of sensitivity experiment terminology, it is applicable in similar fields. The method does assume or require a binary outcome (x = 1 [agitation] or 0 [no agitation]) and that one of the outcomes occurs 100% of the time at the highest level of the stimulus or dose. In our initial study, we assumed that 100% of patients receiving the maximum dose of fentanyl (4.2 µg/kg) would experience no emergence agitation and not that 100% of untreated patients would. An additional condition of this method requires that the probability of the response is an increasing function of the stimuli or dose and the stimuli or dose is normally distributed. We think that our research design met these conditions, and this is why our ED50 of fentanyl worked in subsequent studies.
References
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