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Open AccessJournal ArticleDOI

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

TLDR
mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes, however, definitive clinical data remain elusive.
Abstract
Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches.

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Citations
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Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

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Anesthetic Neurotoxicity — Clinical Implications of Animal Models

TL;DR: The FDA collaboration SmartTots recommends undertaking large-scale clinical studies and avoiding nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age.
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Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

TL;DR: Findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention.
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Executive Function in Children and Adolescents with Critical Cyanotic Congenital Heart Disease

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References
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Journal ArticleDOI

Depth of anaesthesia and post-operative cognitive dysfunction.

TL;DR: Assessment of the possible effect of the level of anaesthesia on post‐operative cognitive dysfunction (POCD) 1 week after surgery, as assessed by a neuropsychological test battery.
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Sevoflurane anesthesia does not impair acquisition learning or memory in the Morris water maze in young adult and aged rats.

TL;DR: The effects of anesthesia with 1 minimum alveolar concentration of sevoflurane for 4 h or sham exposure on cognition were investigated in young adult and aged rats at 1, 4, and 12 weeks postexposure.
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Inhibition of α5 γ-Aminobutyric acid type A receptors restores recognition memory after general anesthesia.

TL;DR: This proof-of-concept study shows that &agr;5GABAA receptors are necessary for the development of postanesthetic deficits in recognition memory and that these receptors can be targeted to restore memory even after the anesthetic has been eliminated.
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Nitrous oxide (N(2)O) requires the N-methyl-D-aspartate receptor for its action in Caenorhabditis elegans.

TL;DR: The behavioral effects of N(2)O require the NMDA receptor NMR-1, consistent with the hypothesis formed from vertebrate electrophysiological data that a major target of N2O is theNMDA receptor.
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Alzheimer's disease and anesthesia.

TL;DR: The literature linking anesthesia to Alzheimer's disease is reviewed, with a focus on the biochemical consequences of anesthetic exposure on AD pathogenic pathways.
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