Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar
Vesna Jevtovic-Todorovic,Anthony Absalom,Klas Blomgren,Ansgar M. Brambrink,G. Crosby,Deborah J. Culley,Gary Fiskum,Rona G. Giffard,Karl F. Herold,Andreas W. Loepke,Daqing Ma,Beverley A. Orser,Emmanuel Planel,W. Slikker,Sulpicio G. Soriano,G. Stratmann,Laszlo Vutskits,Zhongcong Xie,Hugh C. Hemmings +18 more
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.read more
Citations
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Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial
Andrew Davidson,Nicola Disma,Jurgen C. de Graaff,Davinia E. Withington,Liam Dorris,Graham Bell,Robyn Stargatt,Robyn Stargatt,David C. Bellinger,David C. Bellinger,Tibor Schuster,Sarah J Arnup,Pollyanna Hardy,Rodney W. Hunt,Rodney W. Hunt,Michael Takagi,Gaia Giribaldi,Penelope L Hartmann,Ida Salvo,Neil S. Morton,Britta S von Ungern Sternberg,Britta S von Ungern Sternberg,Bruno Guido Locatelli,Niall C. T. Wilton,Anne M. Lynn,Joss J. Thomas,David M. Polaner,Oliver Bagshaw,Peter Szmuk,Anthony Absalom,Geoff Frawley,Charles B. Berde,Gillian D Ormond,Jacki Marmor,Mary Ellen McCann +34 more
TL;DR: This trial found no evidence that just under an hour of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at two years of age compared to RA.
Journal ArticleDOI
Clinical Pharmacokinetics and Pharmacodynamics of Propofol.
TL;DR: An overview of the PK and PD of propofol is provided in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.
Journal ArticleDOI
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.
Journal ArticleDOI
Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.
Danqing Hu,Randall P. Flick,Michael J. Zaccariello,Robert C. Colligan,Slavica K. Katusic,Darrell R. Schroeder,Andrew C. Hanson,Shonie L. Buenvenida,Stephen J. Gleich,Robert T. Wilder,Juraj Sprung,David O. Warner +11 more
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.
Journal ArticleDOI
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
Isoflurane impairs immature astroglia development in vitro: the role of actin cytoskeleton.
Nadia Lunardi,Christoph Hucklenbruch,Janelle R. Latham,Joseph R. Scarpa,Vesna Jevtovic-Todorovic +4 more
TL;DR: Isoflurane-induced actin cytoskeletal changes were accompanied by a significant decrease in protein levels of the endogenous GTPase RhoA that regulates the phosphorylation of myosin light chain protein, suggesting that isoflurane -induced impairment in glial growth and morphological development is, in part, mediated by the RHoA/myosinLight chain protein signaling pathway.
Journal ArticleDOI
Heat Shock Protein 72 Overexpression Prevents Early Postoperative Memory Decline after Orthopedic Surgery under General Anesthesia in Mice
TL;DR: Hsp72 overexpression is associated with prevention of postoperative hippocampal-dependent and -independent memory deficit induced by anesthesia and/or surgery and is not correlated with numbers of activated hippocampal microglia.
Journal ArticleDOI
Isoflurane Preconditioning Elicits Competent Endogenous Mechanisms of Protection from Oxidative Stress in Cardiomyocytes Derived from Human Embryonic Stem Cells
Ana Sepac,Filip Sedlic,Karim Si-Tayeb,John Lough,Stephen A. Duncan,Martin Bienengraeber,Frank Park,Jinhee Kim,Zeljko J. Bosnjak +8 more
TL;DR: The results suggest a promising ability of APC to protect and improve engraftment of hESC-derived cardiomyocytes into the ischemic heart and potentially other treatments/diseases.
Journal ArticleDOI
Isoflurane affects the cytoskeleton but not survival, proliferation, or synaptogenic properties of rat astrocytes in vitro
Deborah J. Culley,E. K. Cotran,E. Karlsson,Arvind Palanisamy,Justin D. Boyd,Zhongcong Xie,G. Crosby +6 more
TL;DR: Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses.
Journal ArticleDOI
THE GLUTAMINERGIC, GABAergic, DOPAMINERGIC BUT NOT CHOLINERGIC NEURONS ARE SUSCEPTIBLE TO ANAESTHESIA-INDUCED CELL DEATH IN THE RAT DEVELOPING BRAIN
TL;DR: It is suggested that anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neuron in the basal forebrain.
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