Faced with mounting evidence that general anesthesia may impair brain development in babies and young children, experts said Wednesday that more research is greatly needed and that when planning surgery for a child, parents and doctors should consider how urgently it is required, particularly in children younger than 3 years.
In the United States each year, about amillion children younger than 4 have surgery with general anesthesia, according to the Food and Drug Administration.
So far, the threat is only a potential one; there is no proof that children have been harmed. The concern is based on two types of research. Experiments in young monkeys and other animals have shown that commonly used anesthetics andsedatives can kill brain cells, diminish learning and memory and cause behavior problems. And studies in children have found an association between learning problems and multiple exposures to anesthesia early in life — though not single exposures.
But monkeys are not humans, and association does not prove cause and effect. Research now underway is expected to be more definitive, but results will not be available for several years.
original article
NEJM
Anesthetic Neurotoxicity — Clinical Implications of Animal Models
- Article
- References
- General anesthetic and sedative drugs are administered to millions of infants, toddlers, and preschool children each year to facilitate life-saving surgery and other essential surgical or medical procedures. In the past two decades, mounting data from animal and observational human studies have raised concerns that general anesthetics may cause neurotoxic changes in the developing brain that lead to adverse neurodevelopmental outcomes later in life. To address the growing concern about the potential adverse consequences of general anesthesia in young patients, in 2009 the Food and Drug Administration (FDA) established a public–private partnership with the International Anesthesia Research Society (IARS) called Strategies for Mitigating Anesthesia-Related Neurotoxicity in Tots, or SmartTots.1In 2012, the FDA, SmartTots, and the American Academy of Pediatrics released a consensus statement that summarized the state of knowledge and presented several key recommendations. Although there were insufficient data at that time to draw any firm conclusions about an association between exposure to anesthetics and subsequent learning disabilities in children, the consensus statement recommended that elective surgical procedures performed under anesthesia be avoided in children less than 3 years of age. The statement also called for further research to better define the risk. Various nonclinical studies have been undertaken since then, and on the basis of their results, the consensus statement is now being revised to convey a heightened level of concern.More specifically, since the original statement was released, new studies have confirmed that commonly used anesthetics and sedatives that either increase inhibitory γ-aminobutyric acid (GABA) receptor activity (e.g., propofol, etomidate, sevoflurane, desflurane, and isoflurane) or block excitatory glutamate receptors (e.g., ketamine) produce profound neurotoxic effects in laboratory animals.2 The injectable anesthetic propofol, most commonly used to induce a rapid loss of consciousness, causes apoptosis of neurons and oligodendrocytes in the brains of fetal and neonatal macaque monkeys.3 Similarly, the commonly used inhaled anesthetic isoflurane induces widespread apoptosis in the neonatal primate brain. The glutamate receptor antagonist ketamine, when administered as a single dose over a prolonged period (24 hours) during a sensitive phase of brain development, causes long-lasting deficits of memory and attention in primates.4 Studies involving species ranging from nematodes to nonhuman primates have revealed histologic changes and, in some cases, impaired performance on behavioral tests.2 Factors that influence the extent of injury include age at the time of drug exposure and cumulative anesthetic dose.2 Histologic changes include widespread apoptosis and cell death, a reduction in the number of synapses, changes in neuronal morphology, and impaired neurogenesis in the hippocampus.
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