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
Short-term Memory Impairment after Isoflurane in Mice Is Prevented by the α5 γ-Aminobutyric Acid Type A Receptor Inverse Agonist L-655,708
Bechara J. Saab,Ashley J. B. MacLean,Marijana Kanisek,Agnieszka A. Zurek,Loren J. Martin,John C. Roder,Beverley A. Orser +6 more
TL;DR: It is postulated that inhibiting the activity of &agr;5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period, suggesting that an isofLurane interaction at &agR;5gabAA receptors contributes to memory impairment during theEarly postanesthetic period.
Journal ArticleDOI
Cell Age–Specific Vulnerability of Neurons to Anesthetic Toxicity
Rylon D. Hofacer,Meng Deng,Meng Deng,Christopher G. Ward,Bernadin Joseph,Elizabeth A. Hughes,Connie L. Jiang,Steve C. Danzer,Andreas W. Loepke +8 more
TL;DR: Key aspects of the anesthetics phenomenon remain unclear, such as why certain neurons die, whereas immediately adjacent neurons are seemingly unaffected, and why the immature brain is exquisitely vulnerable, whereas the mature brain seems resistant.
Journal ArticleDOI
The effects of isoflurane and desflurane on cognitive function in humans.
Bin Zhang,Ming Tian,Yu Zhen,Yun Yue,Janet Sherman,Hui Zheng,Shuren Li,Rudolph E. Tanzi,Edward R. Marcantonio,Zhongcong Xie +9 more
TL;DR: The findings from this pilot study suggest that isoflurane and desflurane may have different effects on postoperative cognitive function, and additional studies with a larger sample size and longer times of follow-up testing are needed.
Journal ArticleDOI
Nociceptive stimuli enhance anesthetic-induced neuroapoptosis in the rat developing brain.
TL;DR: Nociceptive stimulation and prolonged anesthesia produced significantly more apoptosis than prolonged anesthesia alone when administered to neonates during the synaptogenic period.
Journal ArticleDOI
Anesthetic-induced preconditioning delays opening of mitochondrial permeability transition pore via protein kinase C-ε mediated pathway
Danijel Pravdic,Filip Sedlic,Yasushi Mio,Nikolina Vladic,Martin Bienengraeber,Zeljko J. Bosnjak +5 more
TL;DR: The results point to the connection between cytosolic and mitochondrial components of cardioprotection by isoflurane and the importance of APC-activated PKC in delaying mitochondrial permeability transition pore (mPTP) opening.
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