Let's not throw the baby out with the bath water: potential neurotoxicity of anesthetic drugs in infants and children.

Senior Associate in Anesthesia Children's Hospital Recently, Jevtovic-Todorovic and colleagues reported that the rat pups exposed to combination of isoflurane, midazolam and nitrous oxide developed significant neurodegeneration and delayed deficits in learning and memory testing 1. Previous investigations from the same group reported similar patterns of accelerated neurodegeneration in rat pups exposed to NMDA and GABA antagonists and anticonvulsant drugs 2-4. Thereby prompting these authors to claim, " there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain " 5. This issue is of paramount interest to pediatric anesthesiologist and intensivists because it questions the safety of anesthetics used for fetal and neonatal anesthesia. The landmark studies by Anand and Aynsley-Green revealed that neonates undergoing surgical procedures mount a stress response to surgical procedures and provoked a fundamental change in the perioperative care of neonates 6,7. Experimental paradigms of painful stimuli and maternal withdrawal in newborn rat pups have convincingly demonstrated abnormalities in long-term behavior and pain perception 8-10. Prior to Anand and Aynsley-Green's work, the practice of the " Liverpool Technique " which consisted of nitrous oxide and curare was prevalent in the neonatal " anesthesia " circles. Fortunately, anesthetic agents that provide more hemodynamic stability and more precise monitoring techniques have been applied to the surgical neonate. These developments resulted in the current humane practice of administering anesthetics and analgesics even to the most critically ill neonates during and after surgery. Are the findings of Jevtovic-Todorovic and Olney relevant enough to withhold anesthetics from neonates undergoing surgery and painful procedures? Certainly, no parent or anesthesiologist/intensivist would allow neonates or pregnant mother to be exposed to a neurotoxin. However, methodological issues make the interpretation of results in rats questionable in the setting of the administration of anesthetic drugs to humans. Furthermore, cross species differences make the relevance to human neonates even more remote 11. There is no doubt that the developing central nervous system is exquisitely sensitive to the deleterious effects of derangements in the internal milieu 12. In 1972, Dobbing and Sands demonstrated that peak synaptogenesis occurs between the 3 rd and 7 th post-natal week in rats 13. This is equivalent to the period between 25 gestational week and 1 year of age in humans 14 Therefore, non-physiologic exposure to various drugs and stressors (painful stimuli, …