2019-02-01
Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS)
Publication
Publication
An international, multicentre, randomised, controlled equivalence trial
The Lancet , Volume 393 - Issue 10172 p. 664- 677
Background In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal
cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association
between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone
to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early
infancy affects neurodevelopmental outcomes.
Methods In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals
in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than
60 weeks’ postmenstrual age who were born at more than 26 weeks’ gestation and were undergoing inguinal
herniorrhaphy, without previous exposure to general anaesthesia or risk factors for neurological injury. Patients
were randomly assigned (1:1) by use of a web-based randomisation service to receive either awake-regional
anaesthetic or sevoflurane-based general anaesthetic. Anaesthetists were aware of group allocation, but individuals
administering the neurodevelopmental assessments were not. Parents were informed of their infants group
allocation upon request, but were told to mask this information from assessors. The primary outcome measure
was full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence, third
edition (WPPSI-III), at 5 years of age. The primary analysis was done on a per-protocol basis, adjusted for
gestational age at birth and country, with multiple imputation used to account for missing data. An intention-totreat analysis was also done. A difference in means of 5 points was predefined as the clinical equivalence margin.
This completed trial is registered with ANZCTR, number ACTRN12606000441516, and ClinicalTrials.gov,
number NCT00756600.
Findings Between Feb 9, 2007, and Jan 31, 2013, 4023 infants were screened and 722 were randomly allocated:
363 (50%) to the awake-regional anaesthesia group and 359 (50%) to the general anaesthesia group. There were
74 protocol violations in the awake-regional anaesthesia group and two in the general anaesthesia group. Primary
outcome data for the per-protocol analysis were obtained from 205 children in the awake-regional anaesthesia group
and 242 in the general anaesthesia group. The median duration of general anaesthesia was 54 min (IQR 41–70). The
mean FSIQ score was 99·08 (SD 18·35) in the awake-regional anaesthesia group and 98·97 (19·66) in the general
anaesthesia group, with a difference in means (awake-regional anaesthesia minus general anaesthesia) of 0·23
(95% CI –2·59 to 3·06), providing strong evidence of equivalence. The results of the intention-to-treat analysis were
similar to those of the per-protocol analysis.
Interpretation Slightly less than 1 h of general anaesthesia in early infancy does not alter neurodevelopmental
outcome at age 5 years compared with awake-regional anaesthesia in a predominantly male study population.
Additional Metadata | |
---|---|
doi.org/10.1016/s0140-6736(18)32485-1, hdl.handle.net/1765/115356 | |
The Lancet | |
Organisation | Department of Anesthesiology |
M.E. McCann (Mary Ellen), de Graaff, J., L. Dorris (Liam), Disma, N., D. Withington (Davinia), G. Bell (Graham), … A.J. Davidswon (Andrew). (2019). Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS). The Lancet, 393(10172), 664–677. doi:10.1016/s0140-6736(18)32485-1 |