News and Events

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.

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.

IARS is pleased to announce the funding of two new research studies totaling $309,000, aimed at addressing remaining pediatric anesthetic neurotoxicity questions.  IARS, and its generous members and donors, have provided the needed funding to continue the work that the SmartTots initiative began ten years ago in partnership with the FDA.  Since its inception, SmartTots has worked in collaboration with investigators from around the world to make anesthesia and surgery safe for our most vulnerable population.  Recent investigations have provided data demonstrating certainty that anesthetic agents disrupt neurodevelopment in animal models.  However, the evidence in humans continues to be mixed.   The funding of these two new projects will start to unravel some of the remaining quandaries in this important area of research.