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

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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.

Original languageEnglish (US)
JournalAnesthesiology
DOIs
StateAccepted/In press - Oct 5 2016

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Isoflurane
Child Development
Macaca mulatta
Anesthesia
Anxiety
Reflex
Social Environment
Neuroglia
Primates
Anesthetics
Retrospective Studies
Wounds and Injuries

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{fd37e279a37f4026be080eed2833c45e,
title = "Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques",
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.",
author = "Kristine Coleman and Robertson, {Nicola D.} and Gregory Dissen and Martha Neuringer and Martin, {Lauren Drew} and {Cuzon Carlson}, Verginia and Kroenke, {Christopher (Chris)} and Damien Fair and Ansgar Brambrink",
year = "2016",
month = "10",
day = "5",
doi = "10.1097/ALN.0000000000001383",
language = "English (US)",
journal = "Anesthesiology",
issn = "0003-3022",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques

AU - Coleman, Kristine

AU - Robertson, Nicola D.

AU - Dissen, Gregory

AU - Neuringer, Martha

AU - Martin, Lauren Drew

AU - Cuzon Carlson, Verginia

AU - Kroenke, Christopher (Chris)

AU - Fair, Damien

AU - Brambrink, Ansgar

PY - 2016/10/5

Y1 - 2016/10/5

N2 - 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.

AB - 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.

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