Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial

被引：754

作者：

Davidson, Andrew J. ^{[1
,2
,3
,4
]}

Disma, Nicola ^{[5
]}

de Graaff, Jurgen C. ^{[6
]}

Withington, Davinia E. ^{[7
,8
]}

Dorris, Liam ^{[9
,11
]}

Bell, Graham ^{[10
]}

Stargatt, Robyn ^{[12
,13
]}

Bellinger, David C. ^{[14
,15
,16
]}

Schuster, Tibor ^{[17
]}

Arnup, Sarah J.

Hardy, Pollyanna ^{[19
]}

Hunt, Rodney W. ^{[4
,18
,20
]}

Takagi, Michael J. ^{[1
,13
]}

Giribaldi, Gaia ^{[5
]}

Hartmann, Penelope L. ^{[1
]}

Salvo, Ida ^{[21
]}

Morton, Neil S. ^{[10
,22
]}

Sternberg, Britta S. von Ungern ^{[23
,24
]}

Locatelli, Bruno Guido ^{[25
]}

Wilton, Niall ^{[26
]}

Lynn, Anne ^{[27
]}

Thomas, Joss J. ^{[28
]}

Polaner, David ^{[29
,30
]}

Bagshaw, Oliver ^{[31
]}

Szmuk, Peter ^{[32
]}

Absalom, Anthony R. ^{[33
]}

Frawley, Geoff ^{[1
,3
]}

Berde, Charles ^{[34
]}

Ormond, Gillian D. ^{[1
]}

Marmor, Jacki ^{[14
]}

McCann, Mary Ellen ^{[34
]}

机构：

[1] Murdoch Childrens Res Inst, Anaesthesia & Pain Management Res Grp, Melbourne, Vic, Australia

[2] Murdoch Childrens Res Inst, Melbourne Childrens Trials Ctr, Melbourne, Vic, Australia

[3] Royal Childrens Hosp, Dept Anaesthesia & Pain Management, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia

[5] Ist Giannina Gaslini, Dept Anesthesia, I-16148 Genoa, Italy

[6] Wilhelmina Childrens Hosp, Univ Med Ctr Utrecht, Dept Anaesthesia, Utrecht, Netherlands

[7] Montreal Childrens Hosp, Dept Anesthesia, Montreal, PQ H3H 1P3, Canada

[8] McGill Univ, Dept Anesthesia, Montreal, PQ, Canada

[9] Royal Hosp Children, Paediat Neurosci Res Grp, Fraser Allander Unit, Glasgow, Lanark, Scotland

[10] Royal Hosp Children, Dept Anaesthesia, Glasgow, Lanark, Scotland

[11] Univ Glasgow, Mental Hlth & Wellbeing, Glasgow, Lanark, Scotland

[12] La Trobe Univ, Sch Psychol Sci, Bundoora, Vic 3086, Australia

[13] Murdoch Childrens Res Inst, Child Neuropsychol, Melbourne, Vic, Australia

[14] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurol, Boston, MA USA

[15] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Psychiat, Boston, MA USA

[16] Harvard T H Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA

[17] Murdoch Childrens Res Inst, Clin Epidemiol & Biostatist Unit, Melbourne, Vic, Australia

[18] Murdoch Childrens Res Inst, Neonatal Res Grp, Melbourne, Vic, Australia

[19] Univ Oxford, Clin Trials Unit, Natl Perinatal Epidemiol Unit, Oxford, England

[20] Royal Childrens Hosp, Dept Neonatal Med, Melbourne, Vic, Australia

[21] Osped Pediat Vittore Buzzi, Dept Anesthesiol & Pediat Intens Care, Milan, Italy

[22] Univ Glasgow, Glasgow, Lanark, Scotland

[23] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia

[24] Princess Margaret Hosp Children, Dept Anaesthesia & Pain Management, Perth, WA, Australia

[25] Osped Papa Giovanni XXIII, Dept Anesthesia, Bergamo, Italy

[26] Starship Childrens Hosp, Auckland Dist Hlth Board, Dept Paediat Anaesthesia & Operating Rooms, Auckland, New Zealand

[27] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA

[28] Univ Minnesota, Dept Anesthesia, Minneapolis, MN USA

[29] Childrens Hosp Colorado, Dept Anesthesiol, Aurora, CO USA

[30] Univ Colorado, Sch Med, Aurora, CO USA

[31] Birmingham Childrens Hosp, Dept Anaesthesia, Birmingham, W Midlands, England

[32] Childrens Med Ctr Dallas, Dept Anesthesiol, Dallas, TX USA

[33] Univ Groningen, Univ Med Ctr Groningen, Dept Anaesthesiol, Groningen, Netherlands

[34] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA

来源：

LANCET | 2016年 / 387卷 / 10015期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

EARLY EXPOSURE; LEARNING-DISABILITIES; ACADEMIC-PERFORMANCE; CHILDHOOD EXPOSURE; DEVELOPING BRAIN; CELL-DEATH; NEUROTOXICITY; REPAIR; DISORDERS; CHILDREN;

D O I：

10.1016/S0140-6736(15)00608-X

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Background Preclinical data suggest that general anaesthetics affect brain development. There is mixed evidence from cohort studies that young children exposed to anaesthesia can have an increased risk of poor neurodevelopmental outcome. We aimed to establish whether general anaesthesia in infancy has any effect on neurodevelopmental outcome. Here we report the secondary outcome of neurodevelopmental outcome at 2 years of age in the General Anaesthesia compared to Spinal anaesthesia (GAS) trial. Methods In this international assessor-masked randomised controlled equivalence trial, we recruited infants younger than 60 weeks postmenstrual age, born at greater than 26 weeks ' gestation, and who had inguinal herniorrhaphy, from 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand. Infants were randomly assigned (1:1) to receive either awake-regional anaesthesia or sevoflurane-based general anaesthesia. Web-based randomisation was done in blocks of two or four and stratified by site and gestational age at birth. Infants were excluded if they had existing risk factors for neurological injury. The primary outcome of the trial will be the Wechsler Preschool and Primary Scale of Intelligence Third Edition (WPPSI-III) Full Scale Intelligence Quotient score at age 5 years. The secondary outcome, reported here, is the composite cognitive score of the Bayley Scales of Infant and Toddler Development III, assessed at 2 years. 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. This trial is registered with ANZCTR, number ACTRN12606000441516 and ClinicalTrials.gov, number NCT00756600. Findings Between Feb 9, 2007, and Jan 31, 2013, 363 infants were randomly assigned to receive awake-regional anaesthesia and 359 to general anaesthesia. Outcome data were available for 238 children in the awake-regional group and 294 in the general anaesthesia group. In the as-per-protocol analysis, the cognitive composite score (mean [SD]) was 98.6 (14.2) in the awake-regional group and 98.2 (14.7) in the general anaesthesia group. There was equivalence in mean between groups (awake-regional minus general anaesthesia 0.169, 95% CI-2.30 to 2.64). The median duration of anaesthesia in the general anaesthesia group was 54 min. Interpretation For this secondary outcome, we found no evidence that just less than 1 h of sevoflurane anaesthesia in infancy increases the risk of adverse neurodevelopmental outcome at 2 years of age compared with awake-regional anaesthesia. Funding Australia National Health and Medical Research Council (NHMRC), Health Technologies Assessment-National Institute for Health Research UK, National Institutes of Health, Food and Drug Administration, Australian and New Zealand College of Anaesthetists, Murdoch Childrens Research Institute, Canadian Institute of Health Research, Canadian Anesthesiologists ' Society, Pfizer Canada, Italian Ministry of Heath, Fonds NutsOhra, and UK Clinical Research Network (UKCRN).

引用

页码：239 / 250

页数：12

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