Anesthesia and neurodevelopment after 20 years
Where are we now and where to next?
March 2023 by Dr Shona Chung
This extensive editorial starts with the history of research into neurodevelopmental effects of general anaesthesia in children: from the initial study in rats in 2003 to the FDA black box warning in 2016, to a summary of larger trials – GAS, PANDA and MASK which have recently been combined in a meta-analysis. This meta-analysis confirmed that exposure to anaesthesia did not alter FSIQ (full scale intelligence quotient) scores but was related to parental reports of behavioural problems.
Subsequently, the authors comment on a recent study by Moser et all which looks at very preterm infants receiving anaesthesia and how this affects their FSIQ at 3 years of age. They highlight that this retrospective study contributes significantly to the literature as it focuses only on extreme prematurity but also note that there is a significant amount of missing FSIQ data. The study authors have acknowledged and dealt with this “missingness” by using a sophisticated statistical tool – multiple imputed chained equations (MICE). The use of MICE has also inverted the statistical significance of FDA labelled drugs, leading the editorial authors to question how it has affected the other results of the trial.
Finally, Bailey and Whyte ask, “where to now?”, and reinforce the fact that paediatric anaesthesiolgists “must explore all avenues to apply primum non nocere”. They explain the different between the SmartTots and Safetots initiatives: the former being a partnership to fund research into the potential direct neurotoxic effect of anaesthesia medications; the latter focusing more on the quality of anaesthesia management with a lot of their recommendations arising from the NECTARINE study.
The main future directions suggested by the editorial include minimising FDA labelled drug exposure where feasible, more routine use of NIRS, more regular use of novel drugs such as dexmedetomidine and a shift in research from the direct neurotoxic effects of anaesthesia drugs to research focused on observed patterns of neonatal white matter injury in a variety of circumstances.