Emily A Olsen1, Ansgar M Brambrink. 1. aDepartment of Anesthesiology and Perioperative Medicine bDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, USA.
Abstract
PURPOSE OF REVIEW: Sedation and anesthesia are often necessary for children at any age, and are frequently provided in ambulatory settings. Concerns have mounted, based on both laboratory studies including various mammalian species and retrospective human clinical studies, that the very drugs that induce sedation and anesthesia may trigger an injury in the developing brain, resulting in long-lasting neurobehavioral consequences. RECENT FINDINGS: New retrospective studies further augment these concerns. Specifically, recent studies support that a single anesthesia exposure before age 3 may increase the risk for long-term disabilities in language acquisition and abstract reasoning, and that exposure to two or more anesthetics before age 2 nearly doubles the risk for an attention-deficit hyperactivity disorder diagnosis by age 19. However, methodological limitations preclude final conclusions or change in practice based on these reports, as retrospective studies cannot prove causation. Ongoing prospective clinical studies such as 'General Anesthesia and Apoptosis Study', 'Pediatric Anesthesia NeuroDevelopment Assessment', and 'Mayo Safety in Kids' trials will offer more answers in the future. Meanwhile, laboratory experiments continue to describe differential morphologic injury to individual structures in the neuropil, and have identified mitochondrial dysfunction and neuroinflammation as potential links in the injury process. Additionally, concepts for protection against anesthesia-induced neurotoxicity continue to be tested in the laboratory. SUMMARY: Results from ongoing prospective clinical trials and translational research will help clarify whether anesthesia-associated neurotoxicity affects the developing human brain, including whether it causes long-term disability, and may further identify the injury mechanisms and potential strategies for protection. Currently, the available evidence does not support a change in practice.
PURPOSE OF REVIEW: Sedation and anesthesia are often necessary for children at any age, and are frequently provided in ambulatory settings. Concerns have mounted, based on both laboratory studies including various mammalian species and retrospective human clinical studies, that the very drugs that induce sedation and anesthesia may trigger an injury in the developing brain, resulting in long-lasting neurobehavioral consequences. RECENT FINDINGS: New retrospective studies further augment these concerns. Specifically, recent studies support that a single anesthesia exposure before age 3 may increase the risk for long-term disabilities in language acquisition and abstract reasoning, and that exposure to two or more anesthetics before age 2 nearly doubles the risk for an attention-deficit hyperactivity disorder diagnosis by age 19. However, methodological limitations preclude final conclusions or change in practice based on these reports, as retrospective studies cannot prove causation. Ongoing prospective clinical studies such as 'General Anesthesia and Apoptosis Study', 'Pediatric Anesthesia NeuroDevelopment Assessment', and 'Mayo Safety in Kids' trials will offer more answers in the future. Meanwhile, laboratory experiments continue to describe differential morphologic injury to individual structures in the neuropil, and have identified mitochondrial dysfunction and neuroinflammation as potential links in the injury process. Additionally, concepts for protection against anesthesia-induced neurotoxicity continue to be tested in the laboratory. SUMMARY: Results from ongoing prospective clinical trials and translational research will help clarify whether anesthesia-associated neurotoxicity affects the developing human brain, including whether it causes long-term disability, and may further identify the injury mechanisms and potential strategies for protection. Currently, the available evidence does not support a change in practice.
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