To the Editor:
In a recent experimental animal study, Bambrink et al. 1have shown that 5 h of isoflurane anesthesia (0.7–1.5 vol%) in 6-day old primates (Rhesus macaque) caused a large increase in neuronal apoptosis in several brain regions 3 h later. This study adds to a plethora of studies published the last decade showing that exposure of infant animals—primarily rodents—to anesthetic agents, whether N -methyl-d-aspartate receptor antagonist or γ-aminobutyric acid receptor agonist, triggers widespread apoptotic death of neuronal cells in the developing brain. Background information about these studies can be found in a recent review article.2Indeed, these studies have been a subject of intense speculation and debate in the pediatric anesthetic community.3Unfortunately, although human studies are being mounted, they are still scarce, and the results of animal studies and laboratory investigations cannot easily be translated into the human clinical environment because of, for example, pharmacokinetic and pharmacodynamic differences.3
However, at this point, there is solid animal evidence that anesthetic drugs induce acute apoptotic neurodegeneration in the developing animal brain. In our opinion, there is no need for any more animal studies of this kind. These will only add to the current confusion rather than contribute to a move forward. From now on, experimental animal research on this topic should be focused on the long-term morphological and, in particular, the neurocognitive consequences of these findings (if any), as well as a safer use of our anesthetic drugs, including possibly protective strategies. For instance, why did the authors not wait several months or even years before harvesting the brains of the monkeys used in the present study? Apoptosis can be elicited by physiologic and pathologic stimuli. The number of supernumerary neurons disappearing due to physiologic apoptosis during normal brain development has been estimated in human beings and rodents to be 50–70% of the entire neuronal cell population. Therefore, one could expect significant recovery of function because the pathologic process occurs at a time of great neuroplasticity.
Researchers should now focus on human beings and neurocognitive function after exposure to anesthetic agents in infancy and early childhood in various clinical situations; there is no need or reason to sacrifice more animals.
*Odense University Hospital, Odense, Denmark. tomghansen@dadlnet.dk
