Perioperative Medicine  |   January 2017
Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques
Author Notes
  • 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.
  • Submitted for publication October 1, 2015. Accepted for publication September 7, 2016.
    Submitted for publication October 1, 2015. Accepted for publication September 7, 2016.×
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • Corresponding article on page 6.
    Corresponding article on page 6.×
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    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Address correspondence to Dr. Brambrink: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Portland, Oregon 97239. brambrin@ohsu.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Pediatric Anesthesia / Pharmacology
Perioperative Medicine   |   January 2017
Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques
Anesthesiology 1 2017, Vol.126, 74-84. doi:10.1097/ALN.0000000000001383
Anesthesiology 1 2017, Vol.126, 74-84. doi:10.1097/ALN.0000000000001383
Abstract

Background: Experimental 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.

Methods: The 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.

Results: Compared 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.

Conclusions: Neonatal exposure to isoflurane, particularly when repeated, has long-term behavioral consequences affecting both motor and socioemotional aspects of behavior.