SPS Plenary Session May 21, 2019 | 9:00 am | Vesna Jevtovic-Todorovic, MD, PhD, MBA
SPS 2019 Annual Conference attendees experienced a unique opportunity to explore revolutionary research on the topic of anesthetic- and sedative-related neurotoxicity with a pioneer in the field, Vesna Jevtovic-Todorovic, MD, PhD, Professor and Chair of Anesthesiology at Colorado University School of Medicine. Dr. Jevtovic-Todorovic, the recipient of multiple NIH grants and research awards over the past two decades, delivered a sweeping overview of this complex topic. Her work focuses on mechanisms by which anesthetic drugs interact with neurotransmitter systems in the central nervous system to produce both pharmacological and toxicological effects. Her initial studies relating to the neurotoxicity of anesthetics in the developing brain continue to influence investigation into anesthetic-induced neurotoxicity.
She began with a review of synaptogenesis, the miraculous mechanism by which neurons develop branching connections. Over the first three years of life, a human brain grows to contain 80 billion neurons, with as many as 1000 synapses per neuron (exceeding a rate of 800,000 connections per second!). Her research demonstrated that young rodent brains exposed to common anesthetics and sedatives undergo accelerated apoptosis—her pathology slides demonstrated marked changes in neuronal structure after exposure, which her research later correlated with changes in learning behavior (1).
Dr. Jevtovic-Todorovic went on to review research in infants and children exposed to anesthesia at a young age, in particular data from Olmstead County, Minnesota. She summarized work by Wilder et al. (2), demonstrating an association between learning disability and ADHD in children who had been exposed to more than one anesthetic event in the 1980s, and Hu et al. (3), who replicated these results with “present day” anesthetic technique in a smaller cohort of patients.
She subsequently reviewed recent multi-centered human trials evaluating the effect of anesthesia on the development of young children, including the MASK (4) and GAS (5) studies. Although evidence is reassuring that a brief (<1 hour) single exposure to an anesthetic appears not to affect neurocognitive development, at least up until age five years, Dr. Jevtovic-Todorovic pointed out that in the retrospective cohort studies, neurocognitive differences became increasingly apparent beyond age seven years. The full answer to the neurotoxicity question has not yet been determined. The presentation concluded with a mention of dexmedetomidine and the fact that, unlike most common sedatives and anesthetics, this drug doesn’t interfere with GABA and glutamate and doesn’t cause neuro-apoptosis. Dr. Jevtovic-Todorovic expressed hope for the development of less toxic anesthetics in the future. Until that happens, we should be judicious and weigh the risks and benefits of long-term or recurrent sedative exposures.
- Jevtovic-Todorovic V, Hartman RE, Izumi Y et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23(3):876-82.
- Wilder RT, Flick RP, Sprung J, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110(4):796-804.
- Hu D, Flick RP, Zaccariello MJ, et al. Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort. Anesthesiology 2017;127(2):227.
- Warner DO, Zaccariello MJ, Katusic SK, et al. Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study. Anesthesiology 2018 Jul;129(1):89-105.
- McCann ME, deGraff JC, Dorris L, et al. (GAS Consortium). Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet 2019;393(10172):664-677.