J Urol. 2012 Nov 20. [Epub ahead of print]
Hays SR, Deshpande JK.
General anesthetics can induce apoptotic neurodegeneration and subsequent maladaptive behaviors in animals. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes. Relevance of animal data to clinical practice is unclear, and causality underlying observed associations in humans is unknown. Newly postulated neurodevelopmental risks of pediatric anesthesia are reviewed, with discussion of implications for surgical care of children.
Materials and Methods
The MEDLINE®/PubMed® and EMBASE® databases were queried for citations in English on pediatric anesthetic neurotoxicity, with focus on references from the past decade.
Animal studies in rodents and primates demonstrate apoptotic neuropathology and subsequent maladaptive behaviors following exposure to all currently available general anesthetics, with the possible exception of alpha-2-adrenergic agonists. Similar adverse pathologic and clinical effects occur following untreated pain. Anesthetic neurotoxicity in animals develops only following exposure above threshold doses and durations during a critical neurodevelopmental window of maximal synaptogenesis in the absence of concomitant painful stimuli; anesthetic exposure outside this critical neurodevelopmental window, or below threshold doses and durations, is without apparent neurotoxicity, while anesthetic exposure in the context of concomitant painful stimuli is neuroprotective. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes, particularly following multiple exposures. Causality underlying observed associations is unknown. Ongoing investigations may clarify what risks are actually associated with current practice.
Surgical care of all patients mandates appropriate anesthesia. Neurotoxic doses and durations of anesthetic exposure in animals may have little relevance to clinical practice, particularly surgical anesthesia for perioperative pain. Causality underlying observed associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes is unknown: anesthetic exposure may simply be a marker for increased risk. Particularly in young children, procedures requiring general anesthesia should be performed only as necessary, and duration of general anesthesia should be minimized. Alternatives to general anesthesia and deferral of elective procedures beyond the first few years of life as appropriate should be considered. Participation in ongoing efforts to generate further data should be encouraged.
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Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.