• Anesthesiology · Jan 2017

    Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques.

    • Kristine Coleman, Nicola D Robertson, Gregory A Dissen, Martha D Neuringer, L Drew Martin, Verginia C Cuzon Carlson, Christopher Kroenke, Damien Fair, and Ansgar M Brambrink.
    • From the Divisions of Comparative Medicine (K.C., N.D.R., L.D.M.) and Neuroscience (K.C., G.A.D., M.D.N., V.C.C.C., C.K.), Oregon National Primate Research Center, Beaverton, Oregon; and Departments of Behavioral Neuroscience (D.F.) and Anesthesiology and Perioperative Medicine (A.M.B.), Oregon Health and Science University, Portland, Oregon.
    • Anesthesiology. 2017 Jan 1; 126 (1): 74-84.

    BackgroundExperimental evidence correlates anesthetic exposure during early development with neuronal and glial injury and death, as well as behavioral and cognitive impairments, in young animals. Several, although not all, retrospective human studies of neurocognitive and behavioral disorders after childhood exposure to anesthesia suggest a similar association. Few studies have specifically investigated the effects of infant anesthesia exposure on subsequent neurobehavioral development. Using a highly translational nonhuman primate model, the authors investigated the potential dose-dependent effects of anesthesia across the first year of development.MethodsThe authors examined the effects of single or multiple early postnatal isoflurane exposures on subsequent behavioral development in 24 socially reared rhesus macaques. Infants were exposed to 5 h of isoflurane anesthesia once, three times (ISO-3), or not at all (control). The authors assessed reflex development and anxiety using standardized tests. At approximately 1 yr, infants (n = 23) were weaned and housed indoors with 5 to 6 other subjects. The authors recorded their response to this move and reassessed anxiety.ResultsCompared to controls, animals exposed to repeated isoflurane (ISO-3) presented with motor reflex deficits at 1 month (median [range]: ISO-3 = 2 [1 to 5] vs. control = 5 [3 to 7]; P < 0.005) and responded to their new social environment with increased anxiety (median [range]: ISO-3 = 0.4 bouts/min [0.2 to 0.6]; control = 0.25 bouts/min [0.1 to 0.3]; P = 0.05) and affiliative/appeasement behavior (median [range]: ISO-3 = 0.1 [0 to 0.2]; control = 0 bouts/min [0 to 0.1]; P < 0.01) at 12 months. There were no statistically significant behavioral alterations after single isoflurane exposure.ConclusionsNeonatal exposure to isoflurane, particularly when repeated, has long-term behavioral consequences affecting both motor and socioemotional aspects of behavior.

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