Publications + Presentations + FAQ

Research Articles

November 2019
October 2019

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?
Pediatric Anesthesia October 31, 2019

Influence of general anesthetic exposure in developing brain on cognition and the underlying mechanisms
October 25, 2019

Sedation practices in pediatric patients with acute lymphoblastic leukemia.
Pediatric Blood & Cancer October 18, 2019

Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study.
Journal of Anesthesia October 14, 2019

General anesthetic neurotoxicity in the young: Mechanism and prevention.
Neuroscience & Biobehavioral Reviews October 10, 2019

Cognitive impairment and transcriptomic profile in hippocampus of young mice after multiple neonatal exposures to sevoflurane.
Aging October 3, 2019

Protective Effects of Xenon on Propofol-Induced Neurotoxicity in Human Neural Stem Cell-Derived Models.
Molecular Neurobiology October 2, 2019

The expression of glucose transporters and mitochondrial division and fusion proteins in rats exposed to hypoxic preconditioning to attenuate propofol neurotoxicity.
International Journal of Neuroscience October 2, 2019

Hypoxia, hypercarbia, and mortality reporting in studies of anaesthesia-related neonatal neurodevelopmental delay in rodent models: A systematic review.
European Journal of Anaesthesiology October 2019

LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats.
Journal of Cellular Biochemistry October 2019

Maternal surgery during pregnancy has a transient adverse effect on the developing fetal rabbit brain
American Journal of Obstetrics and Gynecology October 2019

Mild hypothermia ameliorates anesthesia toxicity in the neonatal macaque brain
Neurobiology of Disease October 2019

The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.
International Journal of Neuroscience October 2019

Xenon reduces sevoflurane-induced respiratory depression and neuro-apoptosis in immature rats
British Journal of Anaesthesia October 2019

April 2019
Anesthesia for pediatric ophthalmologic surgery
Journal of American Association for Pediatric Ophthalmology and Strabismus April 14, 2019

Combined spinal/caudal catheter anesthesia: extending the boundaries of regional anesthesia for complex pediatric urological surgery
Journal of Pediatric Urology April 11, 2019

Dexmedetomidine reduced sevoflurane-induced neurodegeneration and long-term memory deficits in neonatal rats
International Journal of Developmental Neuroscience April 5, 2019

Erythropoietin Reduces Neurodegeneration and Long-Term Memory Deficits Following Sevoflurane Exposure in Neonatal Rats
Neurotoxicity Research April 5, 2019

Quantitative ultrasound and apoptotic death in the neonatal primate brain
Neurobiology of Disease April 2, 2019

Assessing Long-term Neurodevelopmental Outcome Following General Anesthesia in Early Childhood: Challenges and Opportunities
Anesthesia & Analgesia April 2019

Caudal epidural blocks in paediatric patients: a review and practical considerations
British Journal of Anaesthesia April 2019

Female rats are more vulnerable to lasting cognitive impairment after isoflurane exposure on postnatal day 4 than 7
British Journal of Anaesthesia April 2019

Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment.
Journal of Anesthesia April 2019

Neuroinflammation in the Developing Brain: Risk Factors, Involvement of Microglial Cells, and Implication for Early Anesthesia
Anesthesia & Analgesia April 2019

Performance on the Operant Test Battery in young children exposed to procedures requiring general anaesthesia: the MASK study
British Journal of Anaesthesia April 2019


What is SmartTots?
SmartTots is a Public-Private Partnership (PPP) between the US Food and Drug Administration (FDA) and the International Anesthesia Research Society (IARS). The mission of this partnership is to coordinate and fund a research program with the goal of ensuring safe surgery for the millions of infants and young children who undergo anesthesia and/or sedation each year.
What is the National Center for Toxicological Research (NCTR)?
NCTR is an internationally recognized research center at the FDA that supports the goal of improving patient and consumer safety. NCTR, along with other centers at the FDA, conducts research to support the scientific basis for the FDA’s regulatory decisions and reduce risks associated with products regulated by the FDA. One of the ways that NCTR helps assess possible risks to human health is to perform animal research studies that investigate the potential for adverse effects and mechanisms of injury following exposure to potentially dangerous chemicals.
How did the concerns about the safety of anesthetic drugs for infants and young children arise?
The FDA’s National Center for Toxicological Research (NCTR), as well as investigators at several universities, conducted research to study the effects of anesthetics on the nervous systems of developing animals. This research demonstrated that exposure to some anesthetics and sedatives caused memory and learning difficulties and other harmful changes in the central nervous systems of some laboratory animals. Currently, inadequate data exist to prove or disprove whether similar effects occur in children. More information on the results of early animal studies is below.
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Consensus Statement

A growing body of evidence from animal studies and observational studies in humans suggests adverse effects on behavior, learning, and memory may result from exposure to anesthetics and sedation during periods of rapid brain development. In June 2014 the International Anesthesia Research Society and US Food and Drug Administration convened a group of experts in anesthesia, pediatric medicine, neuroscience, and patient safety to consider the evidence and what it means for health care providers and parents.  The SmartTots Consensus Statement on the Use of Anesthetic and Sedative Drugs in Infants, Toddlers, and Preschool Children is the result of many hours of deliberation by that diverse group of experts along with feedback from more than 20 stakeholder organizations.

Scientific Presentations

IARS 2015 Annual Meeting and International Science Symposium

Improving Health through Discovery and Education

Neurotoxicity of Anesthetics in the Developing Brain – A Translational Update

Key Summary Points

Neurotoxicity of Anesthetics in the Developing Brain
  1. The major excitatory neurotransmitter, glutamate, and the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), are generally associated with neuronal communication in the adult brain.
  2. In the developing brain, these transmitters play a central role in brain morphogenesis, including synapse formation, proliferation, migration, differentiation and survival of neurons.