News and Events

SmartTots: Building Community and Advocating for Important Research

SmartTots pediatric anesthetic neurotoxicity thought leaders discuss the current status of the field and provide insights into the future of the research. View on YouTube.

Pediatric Anesthetic Neurotoxicity: Finding Ways to Move Forward

Pediatric anesthetic neurotoxicity investigators discuss the state of the research and identify compelling ways to move the field forward. View on YouTube

Pediatric Anesthetic Neurotoxicity: Designing the Proper Study

Pediatric anesthetic neurotoxicity thought leaders ponder the feasibility of designing and conducting studies that successfully isolate the effects of anesthetics from the effects of the procedure or patient’s underlying condition. View on YouTube

Pediatric Anesthetic Neurotoxicity: The Pre-Clinical Journey

Pediatric anesthetic neurotoxicity researchers discuss how pre-clinical studies are providing insight into the mechanisms of neurotoxicity, and the impact on the future of clinical studies. View on YouTube

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SmartTots – Perspectives from the Front Lines

Millions of children undergo surgery annually. Recent studies suggest there may be reason for concern. This video, featuring Dr. Dean Andropoulos, Dr. Peter Davis, and Dr. Caleb Ing, provides a summary as to why research is needed and the type that is needed.

Columbia University Physician Scientist and SmartTots Investigator, Caleb Ing, MD, publishes new findings regarding prenatal exposure to general anesthesia and subsequent risk to the child.

The association between prenatal exposure to general anaesthesia for maternal surgery during pregnancy and subsequent risk of disruptive or internalising behavioural disorder diagnosis in the child has not been well-defined.

Columbia researchers, led by Caleb Ing, MD,  undertook the task to better define the association by linking a nationwide sample of pregnant women to their liveborn infants using the Medicaid Analytic eXtract (MAX, 1999e2013). Multivariate matching was used to match each child prenatally exposed to general anaesthesia owing to maternal appendectomy or cholecystectomy during pregnancy with five unexposed children. The primary outcome was diagnosis of a disruptive or internalising behavioural disorder in children. Secondary outcomes included diagnoses for a range of other neuropsychiatric disorders.

34,271 prenatally exposed children were matched with 171,355 unexposed children in the database. Prenatally exposed children were more likely than unexposed children to receive a diagnosis of a disruptive or internalizing behavioural disorder (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.23e1.40). For secondary outcomes, increased hazards of disruptive (HR, 1.32; 95% CI, 1.24e1.41) and internalising (HR, 1.36; 95% CI, 1.20e1.53) behavioural disorders were identified, and also increased hazards of attention-deficit/hyperactivity disorder (HR, 1.32; 95% CI, 1.22e1.43), behavioural disorders (HR, 1.28; 95% CI, 1.14e1.42), developmental speech or language disorders (HR, 1.16; 95% CI, 1.05e1.28), and autism (HR, 1.31; 95% CI, 1.05e1.64).

Researchers found that prenatal exposure to general anaesthesia is associated with a 31% increased risk for a subsequent diagnosis of a disruptive or internalising behavioural disorder in children. However, caution is advised when making any clinical decisions regarding care of pregnant women, as avoidance of necessary surgery during pregnancy can have detrimental effects on mothers and their children.

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A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity

Anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, however, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of the scoping review conducted by Matthew Thomas Borzage, PhD, and Bradley S. Peterson, MD, was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.  Their review found an unequivocal yes, that most anesthetics cause neurotoxicity, at least in rodents. When trying to determine a definitive answer as to how their findings relate to the human situation, unfortunately that question still remains elusive. The strongest evidence for neurotoxic effects in humans is from multiple exposures, most likely in the domains of attention and disruptive behaviors, and possibly executive functioning, memory, motor skills, and language abilities.

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TREX Trial Milestone – Enrollment is complete!

Pediatric anesthetic neurotoxicity has been a concern of clinicians and investigators for more than 20 years. Hundreds of preclinical studies and dozens of clinical studies including PANDA, GAS, and MASK have been undertaken during this time. The results have been mixed. The TREX (Toxicity Remifentanil DEXmedetomidine) trial began in 2017 and set out to study prolonged anesthetic exposure effects and address an important data gap – whether a dexmedetomidine-based anesthetic is associated with better neurodevelopmental outcomes. The study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicenter, multinational, superiority trial comparing neurological outcome after standard sevoflurane anesthesia with dexmedetomidine/remifentanil, and low dose sevoflurane anesthesia in children aged less than 2 years undergoing anesthesia of 2 h or longer. There are a total of 20 sites enrolling patients: 7 in Australia, 5 in the U.S. and 8 in Italy with a variety of surgeries being studied at each site. The TREX Trial Investigators recently met a major milestone, the completion of enrollment of 450 trial subjects. The study subjects will return at age 3 years for a battery of neuropsychological testing, including general intelligence, language, fine and gross motor skills, behavioral testing and parent behavioral questionnaires. Once complete in the next 2-3 years, the TREX Trial will make an important contribution to the knowledge about the effects of anesthesia in infants and young children; an issue that potentially affects millions of children globally who undergo anesthesia and surgery each year.

SmartTots: 13 Years of Progress

During the 2000’s, preclinical research studies began to find that laboratory animals exposed to commonly used anesthetic and sedative drugs early in life showed changes to the brain and nervous system that interfered with memory and learning.  Additional research during this time set off alarms for the Food and Drug Administration (FDA), parents, and the anesthesia practitioner community. The FDA held its first Advisory Committee hearing on this issue in 2007. As an outcome of that meeting, representatives from the FDA reached out to the International Anesthesia Research Society (IARS) in 2008 with the idea of forming a Public Private Partnership to address these new, startling findings.  IARS was uniquely positioned to partner with the FDA due to its non-political collaborative mission, infrastructure, expertise and commitment to research, education and advancing the specialty.