DOI: 10.12809/hkmj176918
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
EDITORIAL
Response to the Food and Drug Administration warning on
the use of anaesthetics in young children
Silky Wong, FHKAM (Anaesthesiology), FANZCA;
Theresa WC Hui, FHKAM (Anaesthesiology), FANZCA
Department of Anaesthesiology, Queen Mary Hospital,
Pokfulam, Hong Kong
Corresponding author: (huiwct@ha.org.hk)
On 14 December 2016, the US Food and Drug
Administration (FDA) issued a warning that the repeated or lengthy use of
general anaesthetic and sedative drugs in children under 3 years old and
in pregnant women in their third trimester may affect the development of
children’s brains. Warning labels were required to be added to general
anaesthetic and sedative drugs.1
Data from published studies in pregnant and young
animals have shown that the use of general anaesthetics increases the
chance of apoptosis and neurodegeneration in the developing brain.
Persistent memory and learning disabilities have been demonstrated2 3 as
well as increased severity with increasing duration of anaesthesia.4
Certain human studies suggest an association between anaesthesia and
subsequent behaviour or learning issues such as autism, attention-deficit
disorder, and language deficits.5 6 7 Some researchers postulate that even
relatively simple anaesthesia of babies and young children can pose a risk
of neurotoxicity. The question is whether or not we can translate such
animal data to humans and to what extent we should interpret the animal
findings.8
For many years well-designed human studies were
lacking. Data were mainly observational and retrospective, and with too
many confounding factors. There were often conflicting results in
different studies.9 10 Recently, however, more robust human studies have
been published such as General Anaesthesia compared to Spinal anaesthesia
(GAS) study11 and Pediatric Anesthesia NeuroDevelopment Assessment
(PANDA).12 13 The GAS study, which compares children less than 60 weeks’
post-gestational age (but older than 26 weeks’ post gestation) undergoing
hernia surgery under either general anaesthesia or awake regional
anaesthesia, has shown that at the 2-year mark (secondary outcome), there
is no increase in risk of learning disability. This study is ongoing with
its primary outcome being the Wechsler Preschool and Primary Scale of
Intelligence Third Edition Full Scale Intelligence Quotient score at 5
years old. The PANDA study was a sibling-matched cohort observational
study that examined whether anaesthesia exposure in healthy children
younger than 3 years old is associated with an increased risk of impaired
global cognitive function as the primary outcome. Their secondary outcome
was abnormal domain-specific neurocognitive function and behaviour at the
ages of 8 to 15 years. The study found no significant difference between
the exposed and unexposed in terms of both primary and secondary outcomes.
Both studies point towards a slightly more reassuring outlook for
short-duration exposure to anaesthesia in children.
Although a FDA warning on anaesthesia and exposure
to anaesthetic drugs in paediatric, neonatal, and third-trimester pregnant
women has been long expected, the timing of this warning came as a
surprise to many in the paediatric anaesthesia community, particularly in
light of the recent findings of the more sanguine and robust human studies
and no new evidence of detrimental effects of anaesthesia.
Moreover, the FDA uses a cut-off age of 3 years
old. This age limit is highly debatable since there is currently no
evidence to support the use of 3 years as a cut-off or that anaesthesia in
infants older than 3 years will not be harmful; and vice versa. Some use 3
years as a cut-off for the period of rapid neurodevelopment in a child;
nonetheless a few retrospective cohort studies point towards anaesthesia
affecting children of an older age-group.14 15 Many of these concerns are
likely to be applicable to all patients undergoing surgery with those at
the extremes of age being more vulnerable. Duration of surgery and the
extent of tissue trauma, need for blood transfusion, and the choice of
anaesthetic agent are also important variables.
Data from the American Society of Anesthesiologists
(ASA) Closed Claims Project were analysed and revealed that children under
1 year of age with associated disease were at increased risk of major and
minor morbidity.16 Cardiac arrests related to anaesthesia most often
occurred in infants who were ASA status 3 to 5 and undergoing emergency
procedures. Paediatric anaesthesiologists should therefore collaborate
with surgeons to determine the best time for surgery in a child.17 Often,
children need anaesthesia for operations or procedures that should not be
delayed. In these cases, it is easier to balance the detrimental effects
of not having the surgery against the potential risk of anaesthesia. In
non-urgent surgeries that will not affect the child or the outcome of the
operation if postponed until later in life, it is reasonable to discuss
with all parties involved, including their parents or guardians, as to
whether deferring the surgery can be considered in very young children.
Given that perioperative complications are more common in the very
young,18 this is a good general principle that has always been advocated
by those involved in perioperative paediatric care, notwithstanding this
FDA warning.
References
1. FDA Drug Safety Communication: FDA
review results in new warnings about using general anesthetics and
sedation drugs in young children and pregnant women. Available from:
https://www.fda.gov/Drugs/DrugSafety/ucm532356.htm. Accessed Jul 2017.
2. Jevtovic-Todorovic V, Hartman RE, Izumi
Y, et al. Early exposure to common anesthetic agents causes widespread
neurodegeneration in the developing rat brain and persistent learning
deficits. J Neurosci 2003;23:876-82. Crossref
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general anaesthesia on
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Prolonged exposure
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Is a short anesthetic
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