General anesthesia affecting on developing brain: evidence from animal to clinical research
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REVIEW ARTICLE
General anesthesia affecting on developing brain: evidence from animal to clinical research Xinyue Liu1 · Jing Ji1 · Guo‑Qing Zhao1 Received: 31 December 2019 / Accepted: 6 June 2020 © The Author(s) 2020
Abstract As the recent update of General anaesthesia compared to spinal anaesthesia (GAS) studies has been published in 2019, together with other clinical evidence, the human studies provided an overwhelming mixed evidence of an association between anaesthesia exposure in early childhood and later neurodevelopment changes in children. Pre-clinical studies in animals provided strong evidence on how anaesthetic and sedative agents (ASAs) causing neurotoxicity in developing brain and deficits in long-term cognitive functions. However pre-clinical results cannot translate to clinical practice directly. Three well designed large population-based human studies strongly indicated that a single brief exposure to general anesthesia (GAs) is not associated with any long-term neurodevelopment deficits in children’s brain. Multiple exposure might cause decrease in processing speed and motor skills of children. However, the association between GAs and neurodevelopment in children is still inconclusive. More clinical studies with larger scale observations, randomized trials with longer duration exposure of GAs and follow-ups, more sensitive outcome measurements, and strict confounder controls are needed in the future to provide more conclusive and informative data. New research area has been developed to contribute in finding solutions for clinical practice as attenuating the neurotoxic effect of ASAs. Xenon and Dexmedetomidine are already used in clinical setting as neuroprotection and anaesthetic sparing-effect, but more research is still needed. Keywords General anaesthesia · Pre-clinical study · Clinical study · Randomized trial · Neurotoxicity · Cognitive deficit Abbreviations GAs General anaesthesia GABA γ-Aminobutyric acid NMDA N-Methyl-d-asparate CNS Central nerve system FDA US Food and Drug Administration NGF Nerve growth factor TNF Tumour necrosis factor ROS Reactive oxygen species PANDA Pediatric Anaesthesia Neurodevelopment Assessment GAS General anaesthesia compared to spinal anaesthesia MASK Mayo Anesthesia Safety in Kids FSIQ Full-scale intelligence quotient IQ Cognitive function OTB Operant Test Battery * Guo‑Qing Zhao [email protected] 1
Department of Anesthesiology, China–Japan Union Hospital of Jilin University, Changchun, China
PPP Public–private partnership ASAs Anaesthetic and sedative agents
Introduction The advent of the modern general anaesthesia (GAs) made it possible for the advancement of modern complex surgical and diagnostic procedures in seriously ill patients of all age groups. Anaesthetic and sedative reagents affect the central nervous system (CNS) by interacting with neurotransmitters and resolving neuronal integration between different brain regions. Presently widely used anesthetics act by two major mechanisms, (1) increasing inhibition through
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