Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward

Author:

Ing Caleb1ORCID,Warner David O.,Sun Lena S.2,Flick Randall P.,Davidson Andrew J.,Vutskits Laszlo3,McCann Mary Ellen4,O’Leary James5,Bellinger David C.6,Rauh Virginia7,Orser Beverley A.8,Suresh Santhanam9,Andropoulos Dean B.10

Affiliation:

1. Departments of Anesthesiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York; the Department of Anesthesiology, Mailman School of Public Health, Columbia University, New York, New York

2. Departments of Anesthesiology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York; Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York

3. the e Department of Anesthesiology, Pharmacology, Intensive Care, and Emergency Medicine, University Hospitals of Geneva, Geneva, Switzerland

4. the Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston, Massachusetts; the Departments of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, Massachusetts

5. the Department of Anesthesiology, Bon Secours Hospital, Cork, Ireland

6. the Departments of Neurology and Psychiatry, Harvard Medical School, Boston, Massachusetts; Neurology and Psychiatry, Boston Children’s Hospital, Boston, Massachusetts; the Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts

7. the Heilbrunn Department of Population and Family Health, Mailman School of Public Health, Columbia University, New York, New York

8. the Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada

9. the Departments of Anesthesiology and Pediatrics, Northwestern University, Chicago, Illinois

10. the Departments of Anesthesiology and Pediatrics, Texas Children’s Hospital, Houston, Texas

Abstract

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference95 articles.

1. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.;Jevtovic-Todorovic;J Neurosci,2003

2. Lasting impact of general anaesthesia on the brain: Mechanisms and relevance.;Vutskits;Nat Rev Neurosci,2016

3. Food and Drug Administration Drug Safety Communication: FDA approves label changes for use of general anesthetic and sedation drugs in young children [4-27-2017].Available at: https://www.fda.gov/Drugs/DrugSafety/ucm554634.htm. Accessed November 1, 2017.

4. Anesthesia and developing brains: Implications of the FDA warning.;Andropoulos;N Engl J Med,2017

5. Epidemiology of ambulatory anesthesia for children in the United States: 2006 and 1996.;Rabbitts;Anesth Analg,2010

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