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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 500-512 |
| Number of pages | 13 |
| Journal | Anesthesiology |
| Volume | 136 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2022 |
Funding
This group of authors was assembled by SmartTots (San Francisco, California), a public-private partnership between the U.S. Food and Drug Administration (Silver Spring, Maryland) and the International Anesthesia Research Society (San Francisco, California) formed in 2009 to evaluate the possibility of adverse consequences of general anesthesia in young patients. No authors received any renumeration for their involvement in this article. However, any funding of the authors by SmartTots directly or indirectly or by either the Food and Drug Administration or the International Anesthesia Research Society is disclosed. While the International Anesthesia Research Society and Food and Drug Administration have shared interests and activities, they have no financial relationship, and each group is responsible for its own activities and resources. The International Anesthesia Research Society, however, does receive a National Institutes of Health (Bethesda, Maryland) grant from the Food and Drug Administration for specific research and administrative activities in support of SmartTots. Dr. Ing received a 1-yr SmartTots research grant in 2012 for the project “Anesthetic Exposure Duration and Effects on Cognitive Language Ability.” Dr. Warner and Dr. Flick received funding from the Food and Drug Administration between 2008 and 2011 (Food and Drug Administration SOL-08-SAFEKIDs CLIN 005–Project 5–Assessment of Long-term Cognitive Development following General Anesthesia as an Infant). Dr. Sun received funding from SmartTots between 2013 and 2016 to support the Pediatric Anesthesia and NeuroDevelopment Assessment (PANDA) Study and a conference grant to support the 2016 PANDA Symposium (New York, New York) and was the Medical Director of SmartTots from 2017 to 2018. She also received funding from the Food and Drug Administration between 2008 and 2011 (Food and Drug Administration SOL-08-SAFEKIDS Clin 004–Project 4) for the PANDA study from 2020 to 2022 (Food and Drug Administration 5U01 FD005936-05, subaward 417811G/UR FAO GR511088) for participation in the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and from 2019 to 2023 (Food and Drug Administration contract 75F40119C10101 for BAA EETWP#31) for the project Neurodevelopmental Outcomes in Infants Receiving Opioid-Replacement Pharmacotherapy for Neonatal Opioid Withdrawal Syndrome. Dr. Sun and Dr. Davidson are also co–editor-in-chiefs of the Anesthesiology section of UpToDate, Riverwoods, Illinois. Dr. McCann received funding from the Food and Drug Administration between 2008 and 2011 (Food and Drug Administration SOL-08-SAFEKIDS Clin 002–Project 2) for the General Anesthesia or Awake–Regional Anesthesia in Infancy (GAS) trial. Dr. Orser and Dr. Suresh serve on the Steering Committee for SmartTots without compensation or reimbursement. International Anesthesia Research Society policy specifically prohibits any payments to Trustees for work related to SmartTots. In addition, they serve as members of the International Anesthesia Research Society Board of Trustees and International Anesthesia Research Society Officers. As trustees, they receive reimbursement for travel expenses on behalf of International Anesthesia Research Society and honoraria for meetings on travel days. As officers, they receive a small stipend in addition to travel reimbursement. Dr. Andropoulos also serves on the Steering Committee for SmartTots without compensation or reimbursement, but his institution receives a partial salary reimbursement for his service as Medical Officer under the Food and Drug Administration grant. Dr. Davidson is an Executive Editor of Anesthesiology , and Dr. Vutskits is an Editor of Anesthesiology . Dr. Orser is also co-director of the Perioperative Brain Health Center (Toronto, Ontario, Canada; http://www.perioperativebrainhealth.com ); is a named inventor on a Canadian patent (2,852,978) and two U.S. patents (9,517,265 and 10,981,954) describing new methods for preventing and treating delirium and persistent neurocognitive deficits after anesthesia and surgery; and also collaborates on clinical studies supported by in-kind software donations from Cogstate Ltd. (New Haven, Connecticut). The other authors declare no competing interests.
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine