By Vesna Jevtovic-Todorovic and Hugh Hemmings
Rapidly mounting animal evidence clearly indicates that exposure to general anaesthesia during the early stages of brain development results in long-lasting behavioural impairments. These behavioural impairments manifest as reduced performance in tests of learning and memory know as cognitive deficits, lack of motivation, and problems with social interactions. Some worrisome similarities are apparent when emerging human data are carefully compared with animal data. For instance, rodent data suggest that although anaesthesia exposure in neonatal animals leads to slow learning in adolescence, completing the task is still attainable. As the animals approach middle age the completion of more complex tasks is not possible, thus creating a wider learning gap when compared to control animals. This suggests impairment of normal mental functions critical to higher cognitive functions such as complex memory.
Some emerging human retrospective data suggest that multiple exposures to anaesthesia during critical stages of brain development in early childhood result in learning disabilities that tend to be first detected in early school-age, but which are more pronounced in late teenage years as the complexity of cognitive tasks increases and competitive pressures mount. Interestingly, when the effect of exposure to morphine during early infancy was examined using standardized IQ testing, it was concluded that the visual analysis component was significantly and consistently impaired when these children were followed for the first 5 years of life. This is a tantalizing observation in view of the fact that the visual analysis test is the best prognostic evaluator of higher-order neurocognitive function and, as such, is the most reliable predictor of the development of higher learning functions as well as the ability to organize thoughts and activities in meaningful sequence, to manage multiple tasks in organized fashion and to make high-level decisions (often referred to as ‘executive’ functions).
While still controversial and unproven, the similarities between animal and human findings suggest that the gap in cognitive abilities caused by early exposure to general anaesthesia widens with age, leading to speculation that anaesthesia initiates a slow but inevitable reduction in cognitive reserve that could prove to be detrimental to higher intellectual performance later in life. Could it be that disturbing the fine balance between neuronal activity and quiescence reflected as action potential spikes on the one side and between excitatory and inhibitory driving forces that determine neuronal activity on the other side during critical stages of neuronal network formation has such long lasting impact on brain functioning? Or put another way, could it be that general anaesthesia initiates slow but inevitable depletion of cognitive reserve that not only prevents children from reaching their full intellectual potential but speeds cognitive decline in late adulthood, a cognitive decline that can lead to early dementia? While these possibilities are far from established, being able to answer such questions with certainty poses a monumental but worthy challenge to modern anaesthesia and neuroscience.
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Vesna Jevtovic-Todorovic, MD, PhD, MBA is Harold Carron Endowed Professor of Anesthesiology and Neuroscience. An internationally recognized neuropharmacologist and the founder of the field, Dr. Jevtovic-Todorovic is an expert in developmental neurotoxicity and pathophysiogy of chronic pain. Hugh C. Hemmings Jr., MD, PhD, FRCA is Distinguished Research Professor in Anesthetic Mechanisms, Professor of Anesthesiology and Pharmacology, and Chair of Anesthesiology at Weill Cornell Medical College, and Anesthesiologist-in-Chief at New York Presbyterian Hospital/Weill Cornell. An internationally recognized neuropharmacologist, Dr. Hemmings is an expert in the synaptic effects of general anesthetics and mechanisms of neuronal signal transduction.
BJA: British Journal of Anaesthesia has published a special issue on anaesthetic neurotoxicity and neuroplasticity, arising from a BJA-sponsored workshop on this topic and guest edited by Hugh Hemmings, Jr and Vesna Jevtovic-Todorovic. You can browse the table of contents and read all content from the issue free online. Founded in 1923, one year after the first anaesthetic journal was published by the International Anaesthesia Research Society, BJA remains the oldest and largest independent journal of anaesthesia.