Preclinical evidence for anaesthesia-induced neurotoxicity.

Preclinical research concerning anaesthesia-induced neurotoxicity was initiated in 1999. A decade later, the earliest clinical observational data showed mixed results in neurodevelopmental outcomes following anaesthesia exposure at a young age. Hence to date, preclinical studies remain the cornerstone of research in this field, primarily because of the vulnerability of clinical observational studies to confounding bias. This review summarises current preclinical evidence. Most studies used rodent models, although non-human primates have also been employed. Across all gestational and postnatal ages, there is evidence that all commonly used general anaesthetics induce neuronal injury (e.g. apoptosis) and cause neurobehavioural impairment (e.g. learning and memory deficits). These deficits were more pronounced when animals were subjected to either repeated exposure, prolonged durations of exposure or higher doses of anaesthesia. To interpret these results in the clinical context, the strengths and limitations of each model and experiment should be carefully considered, as these preclinical studies were often biased by supraclinical durations and a lack of control with regard to physiological homeostasis.