Seminal Pediatric Anesthesia Research Studies

 

Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia

Ing C, DiMaggio C, Whitehouse A, et al. Long-term differences in language and cognitive function after childhood exposure to anesthesia. Pediatrics 2012; 130(3):e476-e485.

Overview

Researchers looked at the association between the use of anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills and behavior at age 10.  The study found deficits in language and abstract reasoning that were associated with the early exposure to anesthesia.

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Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

Flick RP, Katusic SK, Colligan RC, Wilder RT, Voigt RG, Olson MD, Sprung J, Weaver AL, Schroeder DR, Warner DO. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics 2011; 128(5):e1053-e1061. Erratum in Pediatrics 2012; 129(3):595.

Overview

This study compared children who had been exposed to anesthesia and surgery before the age of 2 to children who had not undergone such exposure.  The results showed that repeated exposure to anesthesia and surgery was associated with the later development of learning disabilities, even when health status was taken into consideration.  To a lesser degree, a similar pattern was observed in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program.

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Isoflurane-induced Neuroapoptosis in the Neonatal Rhesus Macaque Brain

 
Brambrink AM, Evers AS, Avidan MS, Farber NB, Smith DJ, Zhang X, Dissen GA, Creeley CE, Olney JW. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology 2010; 112(4):834-41.

Overview

Researchers examined the effect of isoflurane, a commonly used anesthesia, on infant rhesus monkeys that were equivalent in age to a 6-month-old child.  The results showed a 13-fold increase in brain cell death in those animals infused with the anesthesia for five hours over the control group.

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Prolonged Exposure to Ketamine Increases Neurodegeneration in the Developing Monkey Brain

Zou X, Patterson TA, Divine RL, Sadovova N, Zhang X, Hanig JP, Paule MG, Slikker W Jr, Wang C. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 2009; 27(7), 727-31, 10.1016/j.ijdevneu.2009.06.010.

Overview

This study compared shorter and longer durations of ketamine exposure on newborn rhesus monkeys to determine if there is a duration short enough to not cause neuronal harm. The researchers studied exposure at 3 hours, 9 hours and 24 hours; the results showed no brain cell death at the 3-hour exposure – which most closely approximates the length of a human pediatric anesthesia exposure – but did show significant brain cell death at the 9- and 24-hour durations.

 

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Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort

Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, Gleich SJ, Schroeder DR, Weaver AL, Warner DO. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009; 110(4): 796-804.

Overview

This was a population-based, retrospective birth cohort study that compared children who had had exposure to anesthesia under age 4 with those who had not.  It found that a single exposure did not result in an increased risk for learning disabilities compared to the non-exposed group, however two or more exposures did, with increasing exposures resulting in an even greater risk.  The authors note that it is unclear from the data if the anesthesia itself is the contributing factor or if other factors may be at play.

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Ketamine-induced Neuronal Cell Death in the Perinatal Rhesus Monkey

Slikker W Jr, Zou X, Hotchkiss CE, Divine RL, Sadovova N, Twaddle NC, Doerge DR, Scallet AC, Patterson TA, Hanig JP, Paule MG, Wang C. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci 2007; 98(1):145-58.

Overview

This study sought to determine if ketamine-induced brain cell death in rodents extended to primates as well, and if so, the level at which such damage might occur.  Ketamine, a commonly used pediatric anesthesia, was administered for 24 hours at three stages of development – gestational, 5 days and 35 days; similar studies were also performed on 5-day newborns with a 3-hour duration.  Results showed that the gestational and 5-day subjects were more sensitive to the 24-hour exposure than the 35-day subjects; the 3-hour exposure to the 5-day subjects did not result in brain cell death.

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Early Exposure to Common Anesthetic Agents Causes Widespread Neurodegeneration in the Developing Rat Brain and Persistent Learning Deficits

Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003; 23(3): 876-82.
 
 
 

Overview

This study looked at the effect of commonly used pediatric anesthetics on infant rats.  The researchers administered a typical combination of drugs to 7-day-old infant rats for a 6-hour period, and observed widespread brain cell death; deficits in hippocampal synaptic function, which is associated with memory and learning; and memory/learning impairments that persisted into adolescence and adulthood.

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Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain

Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vockler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., and Olney, J. W. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999; 283(5398), 70-4.

 

Overview

Scientists have known that NMDA (glutamate) helps to promote neuronal development, and that this activity is particularly important in early brain development.  This study showed that blockage of glutamate receptors during late fetal and early neonatal life triggers widespread cell death in the developing rat brain.  Researchers noted that the study may have relevance for human infants since certain medications that block glutamate receptors – ketamine and nitrous oxide – are used in pediatric anesthesia.

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