General anesthetics and the developing brain.
OBJECTIVE
General anesthetics and sedatives are used in millions of children every year to facilitate surgical procedures, imaging studies, and sedation in operating rooms, radiology suites, emergency departments, and ICUs. Mounting evidence from animal studies suggests that prolonged exposure to these compounds may induce widespread neuronal cell death and neurological sequelae, seriously questioning the safety of pediatric anesthesia. This review presents recent developments in this rapidly emerging field.


RESULTS
In animals, all currently available anesthetics and sedatives that have been studied, such as ketamine, midazolam, diazepam, clonazepam, propofol, pentobarbital, chloral hydrate, halothane, isoflurane, sevoflurane, enflurane, nitrous oxide, and xenon, have been demonstrated to trigger widespread neurodegeneration in the immature brain. In humans, recent preliminary findings from epidemiological studies suggest an association between surgery and anesthesia early in life and subsequent learning abnormalities.


CONCLUSIONS
Neurodegeneration following exposure to anesthetics and sedatives has been clearly established in developing animals. However, while some of the biochemical pathways have been revealed, the phenomenon's particular molecular mechanisms remain unclear. As the phenomenon is difficult to study in humans, clinical evidence is still scarce and amounts to associative and not causal relationships. Owing to the lack of alternative anesthetics, further animal studies into the mechanism as well as clinical studies defining human susceptibility are both urgently needed.
Istaphanous
George K
GK
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Loepke
Andreas W
AW
D000768:Anesthesia, General / Q000009:adverse effects*; D000777:Anesthetics / Q000009:adverse effects* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D002648:Child; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000633:toxicity; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000187:drug effects
D000777:Anesthetics; D006993:Hypnotics and Sedatives