title: Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.
abstract: Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year.
authors: Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Anesthesiology and Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors: Erica P
authors: EP
authors: Lin
authors: Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors: Jeong-Rim
authors: JR
authors: Lee
authors: Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Anesthesiology and Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States.
authors: Christopher S
authors: CS
authors: Lee
authors: Department of Anesthesiology, Huashan Hospital of Fudan University, Shanghai, China.
authors: Meng
authors: M
authors: Deng
authors: Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States; Department of Anesthesiology and Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, United States; Neuroscience Program, University of Cincinnati, Cincinnati, OH 45267, United States. Electronic address: pedsanesthesia@gmail.com.
authors: Andreas W
authors: AW
authors: Loepke
mesh_terms: D000367:Age Factors; D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*
chemical_list: D000777:Anesthetics
keywords: Anesthesia; Apoptosis; Cognitive impairment; Infant; Neonate; Neurodegeneration