Resources

Publications + Presentations + FAQ

Research Articles

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

March 2019

Anaesthetic neuroprotection in children: does it exist or is it all just bad?
Current Opinion in Anesthesiology March 2019

Effects of non-obstetric surgery under ketamine anaesthesia in the middle stage of pregnancy on cognition in the offspring and underlying mechanisms
British Journal of Anaesthesia March 2019

Sevoflurane-induced learning deficits and spine loss via nectin-1/corticotrophin-releasing hormone receptor type 1 signalling in neonatal mice
British Journal of Anaesthesia March 2019

February 2019

Isoflurane exposure in infant rats acutely increases aquaporin 4 and does not cause neurocognitive impairment
Bosnian Journal of Basic Medical Sciences February 26, 2019

Effects of Perinatal Exposure to Ketamine on the Developing Brain
Frontiers in Neuroscience February 22, 2019

Dexmedetomidine attenuates the neurotoxicity of propofol toward primary hippocampal neurons in vitro via Erk1/2/CREB/BDNF signaling pathways
Drug Design, Development and Therapy February 19, 2019

Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial
The Lancet. February 16, 2019

Neurodevelopment after general anaesthesia in infants
The Lancet. February 16, 2019

Inhibition of microRNA-375 ameliorated ketamine-induced neurotoxicity in human embryonic stem cell derived neurons.
European Journal of Pharmacology February 5, 2019

Fundamentals of fetal toxicity relevant to sevoflurane exposures during pregnancy.
International Journal of Developmental Neuroscience. February 2019

Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice.
Psychopharmacology February 2019

January 2019

Effects of repeated exposure to different concentrations of sevoflurane on the neonatal mouse hippocampus.
Brazilian Journal of Anesthesiology. January – February 2019

Neurotoxicity of anesthetics: Mechanisms and meaning from mouse intervention studies
Neurotoxicology and Teratology January – February 2019

Neurotoxicity of general anesthetics in children: evidence and uncertainties.
Current Opinion in Pediatrics January 31, 2019

Juvenile Rats Show Altered Gut Microbiota After Exposure to Isoflurane as Neonates
Neurochemical Research January 2, 2019

Astragaloside suppresses tumor necrosis factor receptor-associated factor 5 signaling pathway and alleviates neurodegenerative changes in retinal pigment epithelial cells induced by isoflurane.
Journal of Cellular Biochemistry January 2019

A Review of Clinical Poster Presentations at the Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Symposium
Journal of Neurosurgical Anesthesiology January 2019

An Open Label Pilot Study of a Dexmedetomidine-Remifentanil-Caudal Anesthetic for Infant Lower Abdominal/Lower Extremity Surgery: The T REX Pilot Study.
Pediatric Anesthesia. January 2019

Anesthesia and Neurodevelopment in Children: Many Important Questions Remain Unanswered
Journal of Neurosurgical Anesthesiology January 2019

Anesthesia Exposure in Children, Practitioners Respond to the 2016 FDA Drug Safety Communication
Journal of Neurosurgical Anesthesiology January 2019

Developmental Neurotoxicity: An Update
Journal of Neurosurgical Anesthesiology January 2019

Early Developmental Exposure to Repetitive Long Duration of Midazolam Sedation Causes Behavioral and Synaptic Alterations in a Rodent Model of Neurodevelopment
Journal of Neurosurgical Anesthesiology January 2019

Engaging Stakeholders to Promote Safe Anesthesia and Sedation Care in Young Children
Journal of Neurosurgical Anesthesiology January 2019

Epidemiology and Resource Utilization of Simple Febrile Seizure-associated Hospitalizations in the United States, 2003-2012
Journal of Neurosurgical Anesthesiology January 2019

Introduction to “Anesthesia and Neurodevelopment in Children”: A Supplement from the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium
Journal of Neurosurgical Anesthesiology January 2019

Outcomes Research in Vulnerable Pediatric Populations
Journal of Neurosurgical Anesthesiology January 2019

Prolonged Anesthetic Exposure in Children and Factors Associated With Exposure Duration
Journal of Neurosurgical Anesthesiology January 2019

Reaching Parents Through an Online Community
Journal of Neurosurgical Anesthesiology January 2019

Report on the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium, “Anesthesia and Neurodevelopment in Children.”
Journal of Neurosurgical Anesthesiology January 2019

SmartTots Outcomes Workshop 2017: Notes From a Round Table Discussion About Outcome Measures
Journal of Neurosurgical Anesthesiology January 2019

Summary of Preclinical Poster Presentations at the Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Symposium
Journal of Neurosurgical Anesthesiology January 2019

The association between attention deficit hyperactivity disorder and general anaesthesia – a narrative review
Anaesthesia January 2019

Using Neuroimaging to Study the Effects of Pain, Analgesia, and Anesthesia on Brain Development
Journal of Neurosurgical Anesthesiology January 2019

December 2018

Neuroprotective effects of dexmedetomidine against isoflurane-induced neuronal injury via glutamate regulation in neonatal rats.
Drug Design, Development and Therapy December 28, 2018

Electron microscopy techniques employed to explore mitochondrial defects in the developing rat brain following ketamine treatment.
Experimental Cell Research. December 15, 2018

What anesthetic technique should we use in order to prevent alterations in the neuro development over the pediatric population?
Revista de la Facultad de Ciencias Médicas de Córdoba December 12, 2018

Lipidomics reveals a systemic energy deficient state that precedes neurotoxicity in neonatal monkeys after sevoflurane exposure.
Analytica Chimica Acta. December 11, 2018

CORRESPONDENCE: Reply to Ritchie‐McLean, Susanna; Wilmshurst, Sally, regarding their comment “Can population cohort studies assess the long‐term impact of anesthesia in children?”
Pediatric Anesthesia. December 4, 2018

Sevoflurane induces neurotoxicity in the developing rat hippocampus by upregulating connexin 43 via the JNK/c-Jun/AP-1 pathway.
Biomedicine & Pharmacotherapy December 2018

Neurocognitive Impact of Anesthesia in Children
Advances in Anesthesia. December 2018

FAQ

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.

View all of our frequently asked questions

– Click here for PARENTS AND THE PUBLIC
– Click here for HEALTH CARE PROFESSIONALS
– Click here for GENERAL FAQ

Newsletter Archive

2017 Archive

AUGUST 2017

Look for us during 2017 at the following events:

Click here to view all our newsletter articles.

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

Ansgar Brambrink, MD, PhD

Click here to see more scientific presentations.

Key Summary Points

Neurotoxicity of Anesthetics in the Developing Brain

Key Research Points

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