Effect of Repeated Exposure to Sevoflurane on Electroencephalographic Alpha Oscillation in Pediatric Patients Undergoing Radiation Therapy: A Prospective Observational Study

Abstract

Background: Pharmacological tolerance is defined as a decrease in the effect of a drug over time, or the need to increase the dose to achieve the same effect. It has not been established whether repeated exposure to sevoflurane induces tolerance in children. Methods: We conducted an observational study in children younger than 6 years of age scheduled for multiple radiotherapy sessions with sevoflurane anesthesia. To evaluate the development of sevoflurane tolerance, we analyzed changes in electroencephalographic spectral power at induction, across sessions. We fitted individual and group-level linear regression models to evaluate the correlation between the outcomes and sessions. In addition, a linear mixed-effect model was used to evaluate the association between radiotherapy sessions and outcomes. Results: Eighteen children were included and the median number of radiotherapy sessions per child was 28 (interquartile range: 10 to 33). There was no correlation between induction time and radiotherapy sessions. At the group level, the linear mixed-effect model showed, in a subgroup of patients, that alpha relative power and spectral edge frequency 95 were inversely correlated with the number of anesthesia sessions. Nonetheless, this subgroup did not differ from the other subjects in terms of age, sex, or the total number of radiotherapy sessions. Conclusions: Our results suggest that children undergoing repeated anesthesia exposure for radiotherapy do not develop tolerance to sevoflurane. However, we found that a group of patients exhibited a reduction in the alpha relative power as a function of anesthetic exposure. These results may have implications that justify further studies.