Anesthetic-related neurotoxicity in the young and outcome measures: the devil is in the details.

1303 June 2014 T HERE are few issues facing the field that are more concerning and contentious than the possible neurotoxic effects of anesthetics on children. Although laboratory studies report that virtually all commonly used anesthetics invariably induce neurodegeneration in the developing animal brain, observational studies are less conclusive with some reporting an association between exposure to anesthesia/surgery and adverse neurobehavioral outcome, whereas others do not.1 Among the many methodologic problems associated with human studies are the outcome measures available to the investigators.1,2 As virtually all these studies are retrospective, the outcome is not chosen by the investigator and therefore may not provide the most meaningful measure of the cognitive or behavioral effect. In addition, the various neurocognitive outcomes may or may not be comparable as few studies have reported more than a single end point. In this issue of AnEstHEsIology, Ing et al.3 have attempted to provide a structured comparison of outcome measures representative of those found in most studies of this type. similar to their previous publication,4 data from the Raine study, a cohort of 2,868 children born from 1989 to 1992 in Western Australia, were examined for an association between exposure to anesthesia/surgery in children before the age of 3 yr and three different but closely related outcomes including direct neuropsychological testing, International Classification of Diseases, 9th Revision (ICD-9)–coded clinical disorders, and a group test of academic achievement. of the 781 children included, 112 had been exposed to anesthesia/surgery, and among those exposed, the risk of deficits in individual language assessments and ICD-9 codes for language or cognitive disorders was increased. In contrast, exposed and unexposed children did not differ with regard to academic achievement. The authors conclude that these data explain some of the variation in the literature and underscore the importance of the outcome measure when interpreting studies of cognitive function. similar findings have previously been noted in other studies using more than a single measure of neurodevelopment.5 A cursory review of the literature suggests that the majority of studies with negative results use broad measures of academic performance such as group tests of achievement (California Achievement test and Danish standardized test of achievement) and teacher–parent rating scales very similar to that used in this study.6–9 studies using individual tests of cognitive performance have been uniformly positive, commonly in areas of speech and language. The larger studies performed in Europe utilizing group tests (or similar) tend to be negative, whereas smaller studies using individual neurobehavioral tests more frequently are positive. Anesthetic-related Neurotoxicity in the Young and Outcome Measures