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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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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

TL;DR: With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment.
References
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Journal ArticleDOI

Anesthesia-Induced Hyperphosphorylation Detaches 3-Repeat Tau from Microtubules without Affecting Their Stability In Vivo

TL;DR: Results indicate that, in vivo, a subpopulation of tau bound to MTs does not easily dissociate under conditions that extensively phosphorylate tau, and Tau remaining on the MTs under these conditions is sufficient to maintain MT network integrity.
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Spatial memory performance 2 weeks after general anesthesia in adult rats.

TL;DR: In adult rats, previous general anesthesia is not associated with impaired learning 2 wk later, and in fact, previous 1.2% isoflurane-70% nitrous oxide improves maze performance 2 wK later.
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Sevoflurane preconditioning induces neuroprotection through reactive oxygen species-mediated up-regulation of antioxidant enzymes in rats.

TL;DR: Sevoflurane preconditioning reduces infarct size and improved neurobehavioral outcome in a dose-dependent manner through ROS release and consequent up-regulation of antioxidant enzyme activity before ischemic injury in rats.
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Noxious Stimulation Attenuates Ketamine-induced Neuroapoptosis in the Developing Rat Brain

TL;DR: It is suggested that concurrent surgery and procedural pain attenuates ketamine-induced neuroapoptosis, and the administration of ketamine with concurrent noxious stimulation results in the attenuation of the neuroap optotic response.
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Characterization and quantification of isoflurane-induced developmental apoptotic cell death in mouse cerebral cortex.

TL;DR: Prolonged exposure to isoflurane increased neuronal apoptotic cell death in 7-day-old mice, eliminating approximately 2% of cortical neurons, of which some were identified as GABAergic interneurons.
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