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

Abstract

SummaryBackgroundThere 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.MethodsWe 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.FindingsBetween 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).InterpretationFor 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.

Systematic review and meta-analysis comparing outcomes following orchidopexy for cryptorchidism before or after 1 year of age

“…but it provides additional information relating to the safety of orchidopexy before 1 year of age. Neither review, however, has been able to comment on the safety of delivering anaesthesia for orchidopexy before the age of 1 year, with the best evidence in this area being provided instead by the GAS (General Anaesthesia compared to Spinal) trial22. This is a large, high‐quality RCT comparing sevoflurane anaesthesia with awake spinal anaesthesia for inguinal herniotomy in infants with gestational age at birth of more than 26 weeks and postmenstrual age at operation of less than 60 weeks.…”

“…Reasons cited for delaying surgery until boys are older than 12 months were concerns about possible increased rates of postoperative testicular atrophy in younger children and the heightened awareness of possible adverse effects on neurodevelopment of general anaesthesia in very young children. Much of the evidence about effects of anaesthesia on the developing brain come from animal studies; however, there is an increasing body of research investigating possible effects in humans19, 20, 21, 22.…”

A review of paediatric anaesthetic-related mortality, serious adverse events and critical incidents

“…14 Paediatric perioperative risk models can be generated from collaborative databases containing consensus definitions. 41,43 Research is appropriately directed at the potential toxicity of anaesthetic agents, 3,6,7 and at the significance of physiological parameters, 22,25 and will continue to advance the science of paediatric anaesthesia.…”

“…[1][2][3][4][5][6][7] The purpose of this review was to refocus on immediate clinical safety outcomes within 24 hours of anaesthesia ending. 8 There is a significant difference in outcome in developed and developing countries, and the contributory factors are highlighted in this regard.…”

Early‐life single‐episode sevoflurane exposure impairs social behavior and cognition later in life

“…An interim secondary outcome study from one group did not find increased risk of neurodevelopmental outcome at 2 years of age (Davidson et al. 2016), while another group found cognitive impairment in children ages 6–11 years (Stratmann et al. 2014).…”