For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
103
views
38
references
 Top references
cited by
203
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      218
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Neurodevelopmental outcome at two years of age after general and awake-regional anaesthesia in infancy: a randomised controlled trial

      research-article
      Author(s): , MD 1 , 2 , 3 , , MD 4 , , PhD 5 , , BM 6 , 7 , , DClinPsy 8 , 9 , , MBChB 10 , , PhD 11 , 12 , , PhD 13 , 14 , 15 , , PhD 16 , , MBiostat 16 , , MSc 17 , , PhD 3 , 18 , 19 , , PhD 1 , 12 , , MD 4 , , BPsych(Hons) 1 , , MD 20 , , MD 10 , 21 , , PhD 22 , 23 , , MD 24 , , MBBS 25 , , MD 26 , , MD 27 , , MD 28 , , FRCA 29 , , MD 30 , , MBChB 31 , , MBBS 1 , 2 , , MD 32 , , MSc 1 , , MEd 13 , , McCann 32 , The GAS Consortium
      Publication date (Electronic):
      Journal: Lancet (London, England)

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Background

          There is pre-clinical evidence that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia may have an increased risk of poorer neurodevelopmental outcome. This trial aims to determine if GA in infancy has any impact on neurodevelopmental outcome. The primary outcome for the trial is neurodevelopmental outcome at 5 years of age. The secondary outcome is neurodevelopmental outcome at two years of age and is reported here.

          Methods

          We performed an international assessor-masked randomised controlled equivalence trial in infants less than 60 weeks post-menstrual age, born at greater than 26 weeks gestational age having inguinal herniorrhaphy. Infants were excluded if they had existing risk factors for neurologic injury. Infants were randomly assigned to awake-regional (RA) or sevoflurane-based general anaesthesia (GA). Web-based randomisation was performed in blocks of two or four and stratified by site and gestational age at birth. The outcome for analysis was the composite cognitive score of the Bayley Scales of Infant and Toddler Development, Third Edition. The analysis was as-per-protocol adjusted for gestational age at birth. A difference in means of five points (1/3 SD) was predefined as the clinical equivalence margin. The trial was registered at ANZCTR, ACTRN12606000441516 and ClinicalTrials.gov, NCT00756600.

          Findings

          Between February 2007, and January 2013, 363 infants were randomised to RA and 359 to GA. Outcome data were available for 238 in the RA and 294 in the GA arms. The median duration of anaesthesia in the GA arm was 54 minutes. For the cognitive composite score there was equivalence in means between arms (RA-GA: +0·169, 95% CI −2·30 to +2·64).

          Interpretation

          For this secondary outcome we found no evidence that just under an hour of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at two years of age compared to RA.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          Early exposure to anesthesia and learning disabilities in a population-based birth cohort.

          Robert Wilder, Randall P. Flick, Juraj Sprung … (2009)
          Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD). This was a population-based, retrospective birth cohort study. The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota, from 1976 to 1982 and who remained in the community at 5 yr of age were reviewed to identify children with LD. Cox proportional hazards regression was used to calculate hazard ratios for anesthetic exposure as a predictor of LD, adjusting for gestational age at birth, sex, and birth weight. Of the 5,357 children in this cohort, 593 received general anesthesia before age 4 yr. Compared with those not receiving anesthesia (n = 4,764), a single exposure to anesthesia (n = 449) was not associated with an increased risk of LD (hazard ratio = 1.0; 95% confidence interval, 0.79-1.27). However, children receiving two anesthetics (n = 100) or three or more anesthetics (n = 44) were at increased risk for LD (hazard ratio = 1.59; 95% confidence interval, 1.06-2.37, and hazard ratio = 2.60; 95% confidence interval, 1.60-4.24, respectively). The risk for LD increased with longer cumulative duration of anesthesia exposure (expressed as a continuous variable) (P = 0.016). Exposure to anesthesia was a significant risk factor for the later development of LD in children receiving multiple, but not single anesthetics. These data cannot reveal whether anesthesia itself may contribute to LD or whether the need for anesthesia is a marker for other unidentified factors that contribute to LD.
          Article 0 comments Cited 296 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cognitive and behavioral outcomes after early exposure to anesthesia and surgery.

            R Flick, S. K. Katusic, R. Colligan … (2011)
            Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26-3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.
            Article 0 comments Cited 194 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.

              V Jevtovic-Todorovic, David F. Wozniak, Thomas Hartman … (2003)
              Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABA(A) receptor-enhancing properties. To induce or maintain a surgical plane of anesthesia, it is common practice in pediatric or obstetrical medicine to use agents from these two classes in combination. Therefore, the question arises whether this practice entails significant risk of inducing apoptotic neurodegeneration in the developing human brain. To begin to address this problem, we have administered to 7-d-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical plane of anesthesia for 6 hr, and have observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.
              Article 0 comments Cited 167 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 2985213R
                Journal ID (pubmed-jr-id): 5470
                Journal ID (nlm-ta): Lancet
                Journal ID (iso-abbrev): Lancet
                Title: Lancet (London, England)
                ISSN (Print): 0140-6736
                ISSN (Electronic): 1474-547X
                Publication date Nihms-submitted: 8 September 2016
                Publication date (Electronic): 04 November 2015
                Publication date (Print): 16 January 2016
                Publication date PMC-release: 16 January 2017
                Volume: 387
                Issue: 10015
                Pages: 239-250
                Affiliations
                [1 ]Anaesthesia and Pain Management Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
                [2 ]Department of Anaesthesia and Pain Management, The Royal Children’s Hospital, Melbourne, Australia
                [3 ]Department of Paediatrics, University of Melbourne, Melbourne, Australia
                [4 ]Department of Anesthesia, Istituto Giannina Gaslini, Genoa, Italy
                [5 ]Department of Anaesthesia, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
                [6 ]Department of Anesthesia, Montreal Children’s Hospital, Montreal, Canada
                [7 ]Department of Anesthesia, McGill University, Montreal, Canada
                [8 ]Paediatric Neurosciences Research Group, Fraser of Allander Unit, Royal Hospital for Children, Glasgow, Scotland, UK
                [9 ]Mental Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK
                [10 ]Department of Anaesthesia, Royal Hospital for Children, Glasgow, Scotland, UK
                [11 ]School of Psychological Science, La Trobe University, Victoria, Australia
                [12 ]Child Neuropsychology, Murdoch Childrens Research Institute, Melbourne, Australia
                [13 ]Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [14 ]Department of Psychiatry, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                [15 ]Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
                [16 ]Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, Melbourne, Australia
                [17 ]National Perinatal Epidemiology Unit, Clinical Trials Unit, University of Oxford, Oxford, UK
                [18 ]Department of Neonatal Medicine, The Royal Children’s Hospital, Melbourne, Australia
                [19 ]Neonatal Research Group, Murdoch Childrens Research Institute, Melbourne, Australia
                [20 ]Department of Anesthesiology & Paediatric Intensive Care, Ospedale Pediatrico ‘Vittore Buzzi’, Milan, Italy
                [21 ]University of Glasgow, Glasgow, Scotland, UK
                [22 ]School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia
                [23 ]Department of Anaesthesia and Pain Management, Princess Margaret Hospital for Children, Perth, Australia
                [24 ]Department of Anaesthesia, Ospedale Papa Giovanni XXIII, Bergamo, Italy
                [25 ]Department of Paediatric Anaesthesia and Operating Rooms, Starship Children’s Hospital, Auckland District Health Board, Auckland, New Zealand
                [26 ]Department of Anesthesiology, University of Washington, Seattle, Washington, USA
                [27 ]Department of Anesthesia, University of Minnesota, Minneapolis, Minnesota, USA
                [28 ]Children’s Hospital Colorado and University of Colorado School of Medicine, Department of Anesthesiology, Aurora, Colorado, USA
                [29 ]Department of Anaesthesia, Birmingham Children’s Hospital, Birmingham, UK
                [30 ]Children’s Medical Centre Dallas, Department of Anesthesiology, Dallas, Texas, USA
                [31 ]Department of Anesthesiology, University Medical Center Groningen, Groningen University, Groningen, The Netherlands
                [32 ]Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
                Author notes
                Corresponding Author: Andrew J. Davidson, Anaesthesia and Pain Management Research Group, Murdoch Childrens Research Institute, The Royal Children’s Hospital, Flemington Road, Parkville, Victoria, 3052. Australia. andrew.davidson@ 123456rch.org.au Phone Number: +61 (0)3 9345 4008
                Article
                Manuscript ID: NIHMS790283
                DOI: 10.1016/S0140-6736(15)00608-X
                PMC ID: 5023520
                PubMed ID: 26507180
                SO-VID: 211d746d-7e7b-49ce-a969-cb224275514e
                License:

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

                Comments

                Comment on this article

                scite_

                Similar content218

                See all similar

                Cited by201

                See all cited by

                Most referenced authors408

                See all reference authors