Will surgical anesthesia affect my child's brain development?

Liu Hua, a pediatrician at Beijing United Family Hospital, a master of Tianjin Medical University, encountered a situation where a child had an operation.
In addition to worrying about the child's physical recovery, parents were also afraid that anesthesia would cause the child to become unwise.

Will anesthesia affect the child's intelligence? The latest clinical evidence shows that: based on current clinical trials, a single short-time (within 3 hours, especially within 1 hour) general anesthesia surgery has little effect on infants and young children.

Repeated general anesthesia exposure may be related to decreased learning ability, attention deficit hyperactivity disorder (ADHD), etc.
These associations are not necessarily causal.

During this operation, it must be done, otherwise the consequences will be more serious.

For some operations that can be performed at a time of choice, do not do it until the child is over 3 years old.

Worries about the effects of anesthesia on the brain have a long history.
After the emergence of surgical operations, millions of infants and young children with birth defects can live completely healthy lives after surgery.

The invention of anesthesia relieved the pain during the operation, and also allowed modern medicine to better help patients.

Whether anesthesia affects the brain has always been the focus of researchers.

In 2000, Ikonomidou et al.
published a landmark article in Science ("Science" magazine) on the mechanism of alcohol causing Fetal Alcohol Syndrome (FAS).

By giving alcohol treatment to newborn pups during the peak period of brain synapses, they replicated the similar effects of fetal alcohol syndrome, including decreased brain quality and nerve cell apoptosis.

They found that alcohol causes two different mechanisms of apoptosis and degradation of a large number of nerve cells: N-methyl-D-aspartate (NMDA) antagonism, and γ-aminobutyric acid receptor (GABAA) receptor activation.

This research is naturally noticed by anesthesiologists, because the mechanism of action of many anesthetics and sedatives is also produced by one or two of them.

A few years later, a close connection between anesthetics and nerve cell apoptosis has been found in a large number of animal experimental models.

Almost all anesthetics have such effects, including benzodiazepines, propofol, ketamine, nitrous oxide and so on.

So do these animal experiments have the same process in humans? In view of the inherent limitations of animal models, we cannot directly derive the results of animal experiments to humans.
After all, the doses of animal experiments are much higher than the doses accepted by humans.
There are differences in species, drug efficacy and toxic side effects.

Previous studies have drawn different views.
Some retrospective clinical studies believe that infants and young children who have experienced anesthesia at an early stage are a high-risk factor for learning disabilities.

Ing et al.
retrospectively analyzed 300 10-year-old children, all of whom had anesthesia experience before the age of 3, and conducted language tests, cognitive, motor skills, and behavior tests on them.

Children who have received anesthesia are at higher risk of lack of language and abstract reasoning skills than children who have not received anesthesia.

Filick et al.
also conducted a similar survey, comparing children who were exposed to anesthesia before the age of 2 with those who were not exposed.

They believe that the use of multiple anesthetics, rather than a single one, may be an independent risk factor for children's learning disabilities.

Wilder et al.
also found that multiple anesthetics used before the age of 4 are an important risk factor for children's learning disabilities.

There are also some small studies that may have an impact, including a study published by the American Academy of Pediatrics in 2015 that included 106 children (53 vs.
53) who had received general anesthesia before the age of 4, which may be related to long-term language ability and recognition.
Cognitive ability is related to the decrease in the volume of the structure of the brain.

It should be noted that these studies are the results of retrospective analysis and have certain limitations.
It is difficult to rule out that harmful effects are not caused by factors other than general anesthesia, including surgery, hospitalization, and the disease itself. In addition, in addition to the above studies that believe that there are indeed adverse effects on children, there are also a large number of studies that are contrary to the above views.

In 2011, Hansen et al.
retrospectively analyzed 2500 children who underwent inguinal hernia repair in infancy.
Their standardized test scores in the ninth grade were compared with children who were not exposed to any anesthesia.
They found that there was no difference between them and did not think that anesthesia would cause them Learning disabilities.

Hansen later compared more than 700 children who underwent pyloric stenosis repair in infant anesthesia within 3 months of life, and there was no difference in the adolescent academic performance test of children in the control group.

Of course, there are some similar studies that have put forward ideas that may not affect children, so I won’t list them all again.

The highest level of evidence for our clinical evidence-based basis should be a rigorously designed randomized controlled study.

The latest high-level research shows that a single short-term anesthesia is unlikely to cause brain abnormalities.
The three most recently designed and rigorous large-scale prospective clinical trials to evaluate the effects of anesthetics on the neurodevelopment of children are the GAS study (general anesthesia vs.
spinal anesthesia study).
), the PANDA study (the effect of children’s anesthesia on neurological function), and the MASK study (the Mayo children’s anesthesia safety study).
In the past two years, the results of these clinical studies have been published, which also makes us more clear about the effects of general anesthesia on children Potential impact.

GAS is the abbreviation of The General Anesthesia compared to Spinal Anesthesia.
The study was initiated by Andrew J.
Davidson of the Royal Children’s Hospital in Melbourne, Australia.
It is a multi-national, multi-center, double-blind, randomized controlled study.
The only published randomized controlled trial to evaluate the neurotoxicity of anesthetics in children (randomized controlled studies are high-level evidence-based evidence, mostly classified as level I evidence). The study was launched in 2007.
The main content of the study is to compare 722 infants receiving different methods of anesthesia (general anesthesia and local anesthesia), and randomly assign 363 infants to the short-term sevoflurane general anesthesia group (median exposure time is 54 minutes), 359 infants to the awake local anesthesia group (spine and/or sacral anesthesia), they all underwent inguinal hernia repair.

The primary end point of the GAS study is the FSIQ test (Wechsler Intelligence Test) at the age of 5 to assess the impact on IQ development.
The secondary end point has been published in the journal Lancet from October 2015 to January 2016.
on.

The study believes that children with sevoflurane general anesthesia less than 1 hour in infancy have no increase in the adverse consequences of neurological development by the age of 2 compared with children with local anesthesia.

The end point results of the study were also published in The Lancet in February 2019.
The results also showed that general anesthesia less than 1 hour in early infancy will not change the neurodevelopmental results at the age of 5, and will not be lower than the child’s IQ development.

The PANDA study was initiated by the Morgan Stanley Children’s Hospital of Columbia University in New York, USA.
It evaluated children who underwent hernia repair under general anesthesia (time ranging from 20 minutes to 240 minutes, with a median of 80 minutes) under general anesthesia before the age of 3 years.
The exposed siblings, when they were 8-15 years old, had a detailed assessment of their IQ, neuropsychology, and neurocognitive functions in specific areas.

The final results were published in the JAMA magazine in 2016.
The results suggest that there is no statistically significant difference in IQ scores between siblings who received a single anesthesia before the age of 3, with an average IQ difference of 0.
2 points.

There was no statistically significant difference in the secondary outcomes between exposed siblings and unexposed siblings, such as memory ability, attention, visual-spatial function, executive function, language, movement, and processing speed or behavior.

The MASK study, the Mayo Anesthesia Safety in Kids (MASK) study, is a large cohort study initiated by the Mayo Medical Center and included 997 children.
Had a single general anesthesia, received multiple total drunk, 3 situations.

The results were published in 2018, showing that the three groups of children had no difference in IQ between 8-12 years old and 15-20 years old, but compared with children who did not receive anesthesia, children who had undergone multiple general anesthesia had slightly less early growth and development vulnerability The increase, that is, a slight decrease in the speed of handling problems and a slight decrease in fine motor coordination is related to a slight increase in behavioral problems reported by parents.

Parents in the multiple anesthesia group and the single anesthesia group reported more problems with children's executive ability and reading ability.

Based on the results of current clinical studies, the only clinical randomized trial results published so far show that receiving anesthesia has no effect on neurodevelopmental outcomes at the age of 5 years.

Therefore, evidence is provided to support that a single short-term anesthesia is unlikely to cause cognitive or behavioral abnormalities in normally healthy children.

Therefore, it can be considered that: a single short period of general anesthesia seems to have no effect on the child.

Repeated exposure to general anesthesia may be related to decreased learning ability, attention deficit hyperactivity disorder (ADHD), etc.
These associations are not necessarily causal.

Children who require multiple surgeries are more likely to suffer from serious underlying diseases that may affect neurodevelopment.

Based on current research, even though general anesthesia may have some influence on the child's early development, the degree of this influence is also slight.

Therefore, weigh the pros and cons of surgery without being overly anxious.

Untreated pain may also affect the development of children.
On December 14, 2016, the US FDA issued a recommendation document that mentioned that the use of anesthetics and sedatives for pregnant women and children under 3 years of age may have a negative impact on the developing brain.
In particular, repeated anesthesia or prolonged (more than 3 hours) general anesthesia or sedative drugs may have a negative impact on children's brain development. At that time, the FDA recommended that if the operation requires anesthesia for more than 3 hours, medical staff should discuss the potential adverse effects of anesthesia on brain development with pregnant women and parents of young children, and the appropriate time to postpone the operation without harming the health of the child.
Weigh the pros and cons of surgery and the appropriate timing.

However, the FDA also emphasized that children under 3 years of age or fetuses exposed to anesthesia for more than 3 hours will be at risk.
The statement is mainly based on animal experimental data and needs to be further confirmed by clinical studies.
The degree of risk is still unclear.

Due to the lack of clinical evidence, the US FDA revised the warning in April 2017, stating that pregnant women and children under 3 years of age should not postpone medically necessary operations and require surgery to relieve pain and great pressure, especially when faced with life-threatening operations.
Under circumstances, surgery should not be delayed.

Moreover, untreated pain may be harmful to children and their developing nervous system.

Therefore, generally for a single operation in a short period of time, there is no need to worry too much about the impact on the child and worry about it.

For some operations that can be performed at a selectable time, we can do it as far as possible until the child is over 3 years old.

Author's public number: Hua Shao popular science time disseminates the latest and most authoritative evidence-based medicine to everyone