• M Ruth Graham, Marni Brownell, Daniel G Chateau, Roxana D Dragan, Charles Burchill, and Randal R Fransoo.
• From the Department of Anesthesia (M.R.G.) and Department of Community Health Sciences, Manitoba Centre for Health Policy (M.B., D.G.C., R.D.D., C.B., R.R.F.), University of Manitoba, Winnipeg, Manitoba, Canada.
• Anesthesiology. 2016 Oct 1; 125 (4): 667-677.

BackgroundAnimal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain.MethodsThe authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models.ResultsA total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure.ConclusionsThese findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.

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