Anesthetic Toxicity in the Pediatric Brain

For over 150 years of anesthetic practice, it was believed, that, as a general anesthetic wears off, the brain would return to the same state as before the anesthetic. We are now beginning to understand, that this basic premise of anesthetic pharmacology is false. In 2003 Jevtovic-Todorovic(1) presented her sentinel findings, that a combined anesthetic (midazolam, nitrous oxide and isoflurane), administered to 7-day old rats for 6 hours, kills neurons in the developing brain and causes long-term impairment of brain function. They showed that long-term potentiation (LTP) in the hippocampus was impaired in anesthetized rats(1). LTP is a form of synaptic plasticity, often considered the electrophysiologic correlate of learning and memory and the hippocampus is a brain structure important for learning and memory. More importantly yet, these authors demonstrated a progressive deficit in spatial recognition tasks administered both 4 weeks and 4 1/2 months after anesthesia(1). Immediately concern mounted, within the anesthesia community(2-5) and also within regulatory authorities(6), about whether or not these phenomena might apply to humans. Subsequently, it became clear that the histologic data were reproducible, not only in rodents but in virtually every species tested (for review see(7)), including primates(8-10) further heightening the degree of concern about anesthesia in the immature human brain. An FDA advisory committee meeting in 2007 concluded, that no change in clinical practice is justified based on available data(6) and a follow up meeting in March of this year upheld this recommendation.