Pediatric Anesthesia Neurotoxicity

Abstract

Through the years, care of millions of premature infants and young children has resulted in numerous exposures to a variety of anesthetic and sedative agents. These agents, designed to achieve the substantial depth of neuronal inhibition required for complete loss of consciousness and insensitivity to pain, are often a necessary component of successful treatment. However, data collected in animal models over the past decade suggest that general anesthetics damage developing neurons. Emerging animal and human data also suggest an association between early exposure to general anesthesia and long-term impairment of cognitive development. Consequently, the prudence of administering anesthesia to this population is now being scrutinized. Because general anesthesia cannot often be avoided when young children are diagnosed with conditions requiring surgery, or undergo time in intensive care units, the scientific community is focused on gaining a thorough understanding of the mechanisms of action so that we may take full advantage of the beneficial effects of anesthetics and sedatives without potentially devastating neurotoxic outcomes. A distinctive panel of speakers convened during SmartTots: Pediatric Anesthesia Neurotoxicity, a session at the 2011 International Anesthesia Research Society Annual Meeting, to provide an overview of 2 important lines of research. One focused on improving our knowledge of the cellular mechanisms operational in anesthetic-induced developmental neurotoxicity, and another focused on advancing our understanding of anesthesia-related neurobehavioral sequelae in mammalian species exposed to anesthesia during critical stages of brain development. Laszlo Vutskits, MD, PhD, University Hospitals of Geneva and Head, Neuroscience-oriented Anesthesia Research Group, University of Geneva, Switzerland, offered insight into recent experimental work demonstrating that general anesthetics have a major impact on the formation and elimination of synaptic contacts between neurons. The purpose of this presentation, “Beyond Toxicity: General Anesthetics and Synaptogenesis,” was to address (1) major neurodevelopmental events taking place during the brain growth spurt with a special emphasis on synaptogenesis, (2) the role of neural activity during neural network formation, and (3) how general anesthetics, being powerful modulators of neural activity, influence physiological patterns of synaptogenesis in a developmental stage–dependent manner. Vutskits reviewed basic neurobiological doctrines related to the brain growth spurt and recent observations suggesting that general anesthetics might stand as powerful regulators of synaptogenesis and thereby neural plasticity. Vutskits provided the following conclusions: (1) neural activity has a fundamental role during the assembly of the central nervous system; (2) functional properties of developing neural networks are fundamentally different between the early and late stage of the growth spurt, thus emphasizing the need for probing multiple time points; and (3) general anesthetics can rapidly induce developmental stage–dependent, persistent changes in synapse densities. Functional implications and significance of these conclusions remain unclear. Greg Stratmann, MD, PhD, Associate Professor of Clinical Anesthesia and Perioperative Care at the University of California, San Francisco, presented his research investigating whether anesthesia-induced cognitive decline is treatable. During his presentation, Stratmann discussed a conceptual framework of the neurocognitive deficit that may be caused by anesthesia in infancy, the concepts of prevention and treatment of anesthesia-induced neurocognitive decline, and the efficacy of an intervention designed to treat anesthesia-induced neurocognitive decline in rats. Stratmann reviewed his model for environmental enrichment and discussed his findings that the ill effects of anesthesia on brain function, which are apparent later in life, can be overcome when environmental enrichment is instituted up to 3 weeks after exposure to sevoflurane. These findings support the concept that harnessing the brain’s natural ability to adapt to functional demands can modify the course of anesthesia-induced cognitive decline in rats. He emphasized the need to understand if, and how, anesthesia changes brain function both in animals and in humans. Stratmann cautioned that clinical practice should not be changed until we are certain that a change is From the Departments of Anesthesiology and Neuroscience, University of Virginia Health System, Charlottesville, Virginia. Accepted for publication August 10, 2011. Supported by SmartTots. Conflict of Interest: See Disclosures at the end of the article. Reprints will not be available from the author. Address correspondence to Vesna Jevtovic-Todorovic, MD, PhD, MBA, University of Virginia Health System, Medical School/Steele Wing, PO Box 800710, Charlottesville, VA 22908. Address e-mail to VJ3W@hscmail. mcc.virginia.edu Copyright © 2011 International Anesthesia Research Society DOI: 10.1213/ANE.0b013e3182326622