Download Anaesthesia and the Developing Brain (updated 2015)

Association of Paediatric Anaesthetists of
Great Britain and Ireland
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July 2015
Anaesthesia in Babies Infants and Young Children
For over 10 years the scientific community has been aware that exposing infant animals to
general anaesthesia produces identifiable structural changes in the brain. Effects are specific to
the developing brain and have been identified in a number of species, but depend on the type and
dose of drug administered. Some experimental studies do not mirror clinical use as no surgery
was performed and general anaesthesia was continued for several hours or at higher doses than
used for routine surgery in children. Associations between exposure to anaesthetic agents in
young animals and longer-term changes in behavioural development, particularly deficits in
learning and memory tasks, have raised concern regarding the potential for general anaesthetics
to produce detrimental effects in young babies and infants. However, it is difficult to compare
doses of anaesthetic across different species of experimental animals or to match the ages at
which the developing brain of animals or humans are vulnerable to these effects. Nevertheless,
this information has driven many studies to evaluate potential learning and behavioural changes
in children and adolescents who have required anaesthesia and surgery as babies or in the first 4
years of life. The paediatric anaesthesia community both in the UK and abroad have taken this
issue very seriously and are actively involved in individual and collaborative efforts to try to
determine what risk, if any, exposure to anaesthetic drugs has in the young infant and child.
Anaesthesia and surgery is only undertaken when absolutely necessary in children. This is
particularly so in babies and infants when the nature of their disease mandates that surgical
treatment cannot wait until later in life or because it is of an urgent or emergency nature. Surgery
cannot be performed without adequate anaesthesia and analgesia: inadequate anaesthesia impairs
recovery and carries a life threatening risk in itself. Serious complications related to anaesthesia
are rare nowadays with modern day anaesthesia, even in the very young and the very sick. New
technologies in the operating room are used by anaesthetists to continuously monitor the
circulation, oxygen levels and function of other organs to control wellbeing during surgery.
Therefore, while the beneficial effects of anaesthetic agents in ensuring unconsciousness and
minimising the stress of surgery are clear, it is also now important to determine if the anaesthetic
agents themselves have any longer term effects, so that we can balance the benefits against any
potential risks of anaesthesia. If risks are identified, current and future research will determine
the safest ways for minimising or preventing adverse effects.
Resolving this issue with relevant and high quality ethical, research to improve the quality of
current evidence is necessarily difficult. Several approaches are being used simultaneously.
Firstly, there are studies which look back at medical records to identify children who have
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undergone surgery compared with those who have not. These have examined the link between
anaesthesia exposure and subsequent behavioural development or disorders reported by parents,
teachers or from medical records, School performance, or other measures that assess learning
abilities such as IQ. These studies are useful, but can only identify associations with prior
anaesthetic exposure, rather than confirming that the anaesthetic drug has caused the reported
changes. Interpretation is difficult as surgery itself may have an effect, and children who need
prolonged or repeated anaesthetics in early life often have underlying conditions or illnesses that
may also significantly affect their behaviour or may disrupt their school attendance or family
life. To date, these studies have varied greatly in the numbers of children included, the type of
anaesthesia and surgery they required, and the outcomes used to measure potential adverse
effects. It is reassuring that many of the studies to date have not identified an association
between anaesthesia in early life and adverse effects. This includes comparisons of twins, in
whom only one had anaesthesia before 3 years of age. The data from these children, who have
similar genetic and environmental backgrounds, but do not show an identifiable effect of
anaesthetic exposure on intelligence and behaviour, is important, but the numbers involved are
small.
Given that anaesthetic exposure in early life has not been consistently linked to adverse changes
from clinical studies to date, no changes in anaesthetic clinical practice are recommended
currently. Nevertheless, all these studies looking backwards and relating early anaesthesia to
outcome (retrospective studies) have limitations: their sensitivity to identify small differences or
small increases in risk is limited. Therefore, it cannot be said that collectively these studies have
proven conclusively that there is no problem.
The definitive way to determine if anaesthesia in early life can affect neurodevelopmental
outcome would be through carefully controlled planned (prospective) clinical trials, with detailed
assessment of infants for many years after exposure to anaesthetic drugs. The international
“GAS” (general anaesthesia compared to spinal anaesthesia) study is currently following a large
group of children who had surgery and anaesthesia as infants. It is hoped that this and other
ongoing initiatives will give professionals and parents a definitive answer to this concerning
question. In the meanwhile, the Association of Paediatric Anaesthetists of Great Britain and
Ireland have made this, and other documents available on the APAGBI website with articles and
guidance for both professionals and parents (http://www.apagbi.org.uk/safety/safety-statements).
As the evidence unfolds we will update the articles on this site and we will continue to be
available to help interpret the current concerns.
Professor Andrew Wolf
On Behalf of the Association of Paediatric Anaesthetists of Great Britain and Ireland