Publications + Presentations + FAQ


Research Articles

November 2015
May 2015

Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity
Metab Brain Dis, May 13, 2015.

Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: A randomised placebo-controlled experimental in-vivo study
Eur J Anaesthesiol, May 2015.

Apnea after Awake Regional and General Anesthesia in Infants: The General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes, A Randomized Controlled Trial
Anesthesiology, May 30, 2015.

Carbon monoxide modulates Cytochrome Oxidase Activity and Oxidative Stress in the Developing Murine Brain During Isoflurane Exposure
Free Radic Biol Med., May 29, 2015.

Regional anaesthesia in neonates, infants and children: An educational review
European Journal of Anaesthesiology, May 10, 2015.

Predictors of Failure of Awake Regional Anesthesia for Neonatal Hernia Repair: Data from the General Anesthesia Compared to Spinal Anesthesia Study-Comparing Apnea and Neurodevelopmental Outcomes
Anesthesiology, May 14, 2015

Is this your (paediatric patient’s) brain on (anaesthetic) drugs?: The search for a potential neurological phenotype of anaesthesia-related neurotoxicity in humans
European Journal of Anaesthesiology, May 6, 2015.

Anesthesia and the developing brain: a way forward for clinical research
Paediatr Anaesth, May 5, 2015.

Risk of autistic disorder after exposure to general anaesthesia and surgery: A nationwide, retrospective matched cohort study
European Journal of Anaesthesiology, May 5, 2015.

April 2015

Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.
Anesthesiology, April 13, 2015.

Perioperative effects of caudal and transversus abdominis plane (TAP) blocks for children undergoing urologic robot-assisted laparoscopic surgery.
J Pediatr Urol, April 12, 2015.

Neurotoxicity of Generic Anesthesia Agents in Infants and Children: An Orphan Research Question in Search of a Sponsor
JAMA, April 12, 2015.

Only extra-high dose of ketamine affects l-glutamate-induced intracellular Ca2+ elevation and neurotoxicity
Neurosci Res, April 10, 2015.

Is There Evidence for Long-Term Neurocognitive Effects of Sedatives
Pediatric Sedation Outside of the Operating Room: A Multispecialty International Collaboration, April 6,2015.

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood
Anesthesiology, April 4, 2015.

Dexmedetomidine Attenuates Neurotoxicity Induced by Prenatal Propofol Exposure.
J Neurosurg Anesthesiol, April 4, 2015.

Neurodevelopmental implications of the general anesthesia in neonate and infants
Exp Neurol, April 3, 2015.

Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling
Biochem Biophys Res Commun, April 3, 2015.

Oregon Health & Science University: Ansgar Brambrink, MD, PhD
SmartTots, April 2, 2015.

Developmental stage-dependent impact of midazolam on calbindin, calretinin and parvalbumin expression in the immature rat medial prefrontal cortex during the brain growth spurt.
Int J Dev Neurosci, April 2, 2015.


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.