Short-Term Exposure to Anesthesia in Infancy Does Not Affect Neurodevelopment

Anesthesia team preparing an infant for surgery. A nurse anesthetist (CRNA) is ventilating the child while two colleagues are attempting to place intravenous lines..
Researchers reported full results of the 5-year GAS trial, the first randomized controlled trial to assess the effects of general anesthesia in infancy on neurodevelopmental outcomes.

Infants who undergo general anesthesia of <1 hour do not experience poor neurodevelopmental outcomes compared with infants who receive awake-regional anesthesia, according to a study recently published in the Lancet.

This single-blind, randomized controlled trial ( Identifier: NCT00756600) included 722 infants who underwent inguinal herniorrhaphy who were less than 60 weeks old and born after at least 26 weeks of gestation. Infants were recruited from New Zealand, Australia, the Netherlands, Italy, Canada, the United States, and the United Kingdom. Patients were randomly assigned 1:1 to either general anesthesia with sevoflurane or awake-regional anesthesia, with randomization stratified by site/gestational age at birth and performed in blocks of 2 or 4.

The awake-regional group was given an awake-caudal, awake-spinal, or combination anesthetic, while sevoflurane was administered with an oxygen-air mix. Exclusion criteria included current risk factors for neurological damage, previous congenital heart disease that required therapy or surgery, and pre-surgery mechanical ventilation. The study’s secondary outcome and the focus of this report was the Bayley Scales of Infant and Toddler Development III composite cognitive score at age 2. Clinical equivalence was defined as a difference of 5 points in means, and analysis was adjusted for birth gestational age.

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Of the 722 infants recruited for the study, 447 resulted in complete cases (awake-regional group, n=205; sevoflurane group, n=242). The awake-regional group had a Full Scale Intelligence Quotient score of 99.08, while the sevoflurane group had a score of 98.97, with a difference in mean of 0.23 (95% CI, -2.59 to 3.06) between the groups. In the sevoflurane group, anesthesia lasted a median of 54 minutes. Composite adaptive behavior, language, and motor scores also showed evidence of equivalence.

Limitations to this study included the inherent failure rate of awake-regional anesthesia, the imperfect predictive power of Bayley-III for long-term outcomes, the reporting of a secondary outcome, and a sample consisting of 80% male infants.

The study researchers concluded that “this trial found strong evidence that exposure of just less than 1 h to a sevoflurane general [anesthesia] in infancy does not increase the risk of adverse neurodevelopmental outcome at 2 years of age. Although not definitive, this is the strongest clinical evidence to date that sevoflurane general [anesthesia] in infancy does not result in substantial neurotoxicity.”

Disclosures: This study received funding from Pfizer Canada. See source for additional disclosures.


Davidson AJ, Disma N, de Graaff JC, et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016;387(10015):239-250.