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Adaptation of Microelectrode Array Technology for the Study of Anesthesia-induced Neurotoxicity in the Intact Piglet Brain
Published on: May 12, 2018
Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children
1Department of Anesthesiology and Intensive Care -Pediatric Section, Odense University Hospital, Odense C, Denmark; Clinical Institute - Anesthesiology, University of Southern Denmark, Odense C, Denmark.
Insights
Animal studies suggest anesthesia may harm developing brains, but human data remain inconsistent. Current evidence indicates a single anesthetic exposure is likely safe for infants, with no need to alter clinical practice for urgent surgeries.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Numerous animal studies indicate general anesthetics may cause neurodegeneration and synaptic abnormalities during critical brain development periods.
- Findings in rodents and nonhuman primates raise concerns about potential long-term learning and behavioral deficits in children exposed to anesthesia.
- The potential public health implications are significant due to the large number of young children undergoing anesthesia annually worldwide.
Purpose of the Study:
- To review preclinical evidence of anesthesia-related neurotoxicity.
- To focus on and analyze existing human cohort studies investigating the effects of anesthesia on neurodevelopment.
- To assess the current evidence regarding the safety of anesthesia in pediatric populations.
Main Methods:
- Review of animal studies (rodents, nonhuman primates) on anesthetic neurotoxicity.
- Analysis of human cohort studies examining associations between anesthesia/surgery exposure and neurodevelopmental outcomes.
- Synthesis of preclinical and clinical data to evaluate the relevance of animal findings to human infants and children.
Main Results:
- Animal studies consistently show potential neurotoxic effects of anesthetics during early brain development.
- Human studies published to date show inconsistent results, with some indicating an association and others finding no link between anesthesia exposure and adverse neurodevelopmental outcomes.
- Current human data do not confirm the neurotoxic effects observed in animal models; a single brief anesthetic appears safe in infants.
Conclusions:
- While animal data on anesthesia-related neurotoxicity are concerning, they have not been verified in human studies.
- Existing human studies suggest that a single, brief anesthetic exposure is likely safe for infants.
- There is currently no evidence to warrant changes in clinical practice or postponement of urgent pediatric surgeries due to anesthesia concerns.
Abstract:
A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide, these findings could have significant public health implications. So far, relatively few human (cohort) studies focusing on this topic have been published with inconsistent results. While some studies have indicated an association between exposure to anesthesia and surgery, other studies have indicated no such association. Prospective studies are underway, but the result will not be available for several years. This paper reviews some of the preclinical background behind anesthesia-related neurotoxicity but focuses mainly on the human studies so far. It is concluded that although disturbing, the animal data lack verification in humans. Fortunately, the humans studies performed so far have been unable to confirm these animal data. A single brief anesthetic seems safe in infants. Multiple anesthetic and surgical exposures on the other hand are different. But there may be other reasons for this than merely the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children.
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