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BIOMEDICAL

ANESTHESIA
The Autistic Child
By Sym C. Rankin, RN, CRNA

Sym C. Rankin, RN, CRNA, is a graduate of the son’s journey of recovery led to Sym’s realization that
University of Southwestern Louisiana and the Charity mainstream medicine is far more interested in merely
Hospital School of Nurse Anesthesia (New Orleans). As a treating symptoms than in asking the difficult questions
practicing anesthetist for over 25 years, she has witnessed of why those symptoms exist. She recently joined the
an alarming increase in chronic and autoimmune diseases. practice at True Health Medical Center in Naperville,
Those observations became less academic and more Illinois, and hopes that she can help other families on the
personal after her son was diagnosed with autism. Her same journey.

T
his article represents my educated The trends I have seen should come care, and involving parents).
observations as an experienced as no surprise because autism spectrum The typical anesthesia provider is
nurse anesthetist who also happens disorders have reached epidemic numbers, aware of the behavioral problems in our
to be the mother of a child on the road and autistic children tend to have health children and will do anything to make
to recovery from an autism spectrum problems. I am seeing an increase in the anesthetic experience as smooth as
disorder (ASD). I am also a practitioner the number of these children needing possible. Most anesthesia providers will
taking care of autistic children, so I look at radiological procedures such as an MRI or have a preoperative telephone interview
these issues from a different perspective a CT scan as well as increasing numbers of to discuss our children’s needs. They will
than my anesthesia peers. The following autistic children for various ENT and dental minimize waiting times, provide quiet areas,
observations suggest a need to take heed procedures. and be very open to parental involvement.
of certain issues that might have an impact I am not the only one who has observed But that provider may not realize that
on the delivery of anesthesia in individual these trends. Recently, my profession has he or she needs to look at the metabolic
cases and also suggests a need for rigorous begun to address the special considerations problems in autistic children and consider
study of the potential problems autistic of autistic children and children with how those problems may affect anesthetic
individuals may have when undergoing behavioral problems. They are called choice.
anesthesia. “difficult pediatric patients.”1 This is a new Anesthesia providers generally are aware
As a practicing anesthetist for over 25 term in my profession; we didn’t need such of the prevalence of diagnosed ADHD and
years, I have been in a position to observe a phrase 25 years ago when I started my the various drugs those children may be
trends in the patients I help treat. In recent career. on. They understand that autistic children
years, I have seen an increase in children in A recent educational review article2 may also be on stimulant or antipsychotic
the operating room for various procedures. discussed anesthetic considerations for drugs; therefore, they must regard specific,
A disproportionate number of those cerebral palsy patients, based primarily necessary anesthetic considerations. For
children have diagnosed developmental on their physical problems (e.g., risk for example, when some of these drugs are
delays and behavioral problems in addition aspiration, difficulties positioning the combined with certain anesthetic drugs,
to their medical problems. There are patient, and interactions with anti-spastic an increase in central nervous system
no available statistics to quantify the and anti-epileptic medications). Autistic depression may result. Thus, the anesthesia
numbers, but my anecdotal observations children, on the other hand, were primarily provider knows to avoid or minimize use of
tell me that children need anesthesia in looked at from a behavioral standpoint the problematic agent. But the anesthesia
numbers that would have shocked us a (e.g., minimizing waiting time, providing provider who sees that as the only concern
decade or more ago. quiet areas for pre- and post-operative is missing something very important.

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Many parents tell me their child was the procedures under review in the
different or regressed after an anesthetic. Olmsted County study were halothane
To those of us who have taken a hard look and nitrous oxide. Halothane is a very
at the biochemical problems underlying fat-soluble drug that is difficult for the
our children’s autistic manifestations, liver to metabolize. Nitrous oxide can
those anecdotal reports should come as deactivate methionine synthase, which
no surprise. An anesthetic may represent is a B12 dependent enzyme important in
yet another toxic insult our children get the methylation cycle. What we can learn
exposed to. Therefore, we must help from that study is that administering a
anesthesia providers understand the fat-soluble toxin, followed by inhibition of
physical and biomedical problems our DNA methylation, may result in “learning
children have so that the providers may disabilities.” Although use of halothane
minimize the insults. Not surprisingly, part and nitrous oxide is not as common as it
of the problem is the same mindset we see used to be, it is not a terribly great leap to
in the mainstream medical community at hypothesize that use of similar chemicals
large. and toxins may play a role in triggering or
Mainstream physicians generally react exacerbating manifestations of ASD.
to the physical problems of ASD children All that being said, anesthesia is
in the way their training taught them. unavoidable for children who need to
Clinicians use pharmaceutical drugs to undergo surgical procedures. The goal
manage behaviors, without looking at preferred drugs for anesthetizing autistic in such cases is to minimize the risk. To
what might be causing those behaviors. children.” Although it was true (at least do that, the anesthesia provider must be
Because most anesthesia providers are when the article was written) that there made aware of the unique problems your
very much part of the mainstream, they were no studies directly examining the child has.
see only “autistic” behaviors, and they impact of anesthesia on children with ASD,
try to compensate for those behaviors by there is published data that cautions about In general, these are the things your
sedating the child. Such a provider does using particular agents with patients who anesthesiologist does not know:
not understand the metabolic problems have certain metabolic problems. Many
underlying those behaviors. So, they will of those metabolic problems are the same  Your child has a medical disease —
default to protocols that may include drugs physical problems that, depending on one’s not some mysterious mental disease
that might cause problems. point of view, are underlying many autistic that is solely genetic in origin.
It’s hard to blame the anesthesia manifestations (or at least would be labeled
community for its blindness, considering comorbidities).  Your child may have gastrointestinal
the lack of any professional guidance and Recently published research supports the dysfunction, immune system
resources. The Autism Research Institute potential for problems5. A retrospective dysregulation, inflammation,
(ARI) has two articles devoted to concerns study based on medical and school records mitochondrial dysfunction, heavy
with anesthesia on its Web site. The first 3 from over 5,000 children born between metal poisoning, oxidative stress,
provides both a good general overview of 1976 and 1982 in Olmstead County, and chronic inflammation.
anesthesia for parents and some general Minnesota, found that one exposure to
advice to anesthesia providers. Although anesthesia was not harmful. More than  Most importantly, your child
the advice is accurate to a point, it fails to one exposure, however, doubled the risk probably has impaired detoxification
warn of specific problems autistic children that a child would be identified as having systems and may not be able to
may encounter with anesthetic drugs. a learning disability before the age of 19. metabolize drugs efficiently.
The second ARI article addresses That risk increased with a longer duration
In basic terms, anesthesia consists of
anesthesia for dental procedures 4 . The of the anesthetic. The exposures were
three distinct elements controlled by
author states, “There are no data that between birth and four years of age: a very
pharmaceutical agents:
any anesthetic drugs cause or worsen critical time of brain development.
autism, nor are there any published data on The anesthetics primarily used in  Amnesia (i.e., the patient is asleep
and remembers nothing);
An anesthetic may represent yet another toxic insult
our children get exposed to. Therefore, we must help  Analgesia (i.e., the patient feels no
pain); and
anesthesia providers understand the physical and
biomedical problems our children have so that the  Muscle relaxation (i.e., the patient
providers may minimize the insults. doesn’t move).

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BIOMEDICAL
There is no single agent to handle all
three elements, so a combination of drugs Special attention must be
must be used. The anesthesia provider paid to the use of nitrous
titrates the drugs to effect a proper
balance, taking into account the unique oxide.
condition of the patient. (Indeed, because
anesthesiologists and nurse anesthetists sedation in dental procedures. In addition,
are used to taking unique biochemical it is used on occasion as a carrier gas with
factors into account for each patient, you sevoflurane in mask inductions. That is,
may find it easier to discuss your child’s nitrous oxide is utilized for a second-gas
condition with them than you have with effect to increase the concentration of
other mainstream physicians.) another inhaled anesthetic agent, thereby
Anesthesia is generally administered allowing the patient to get to sleep faster.
through two methods: intravenous also been raised regarding a potential In the last decade, various concerns
and mask induction of gas. For adult for propofol to exacerbate mitochondrial have been raised about the use of nitrous
patients, an IV is started, and usually disease. Unfortunately, however, all oxide: inactivation of methionine synthase,
a sedative and/or narcotic is given as a general anesthetics have a tendency to increase of post-operative nausea,
premedication. Then an induction agent is inhibit mitochondrial function. Moreover, relatively poor amnesic properties, and
given to put the patient to sleep. Propofol the documented difficulties noted with even contribution to greenhouse gasses.
is often used as the induction agent. Then propofol stem from long-term use in the Because of these concerns, nitrous oxide
the airway is secured and an anesthetic gas ICU setting, exceeding the exposure most use in the operating room has dramatically
is used to keep the patient asleep. Often a patients would encounter6 . declined in recent years and will likely
narcotic is added for pain relief. Under most circumstances, propofol approach zero in the coming years.
Sometimes using an intravenous can be safely used. But if there is a That being said, nitrous oxide is still
catheter is possible for children, but more concern about its use, your provider may being used (especially in the dental
often that access is not easily obtained and determine that inhalation induction may setting) and may present specific
an inhalation induction is used instead. A be appropriate using sevoflurane. Only problems for autistic children with
high flow rate is used for the gas, which two-to-five percent of sevoflurane is common underlying conditions. Nitrous
is delivered through a mask on the child. metabolized in the body, making it an oxide depletes the B12/folate system. It
After a few breaths, the child is asleep, IV excellent choice for many patients. (An deactivates methionine synthase, which is
access is able to be obtained, the airway older inhalant, halothane, is rarely used an enzyme that catalyzes the conversion of
is secured, and gas is used to maintain the now because of its tendency to be heavily homocysteine and methyltetrahydrofolate
anesthetic. metabolized.) to methionine and tetrahydrofolate. Such
When you meet with your Sometimes the provider may want a deactivation in a patient with a defect
anesthesiologist or nurse anesthetist, to use ketamine. It is a dissociative in the MTHFR (methylenetetrahydrofolate
be prepared to discuss the methods of anesthetic; in essence, it is a reductase) gene, which is associated with
anesthesia delivery and the exact drugs he hallucinogenic. It is usually used for diminished enzyme activity, could result in
or she intends to use. Do not be afraid to sedation, especially for short procedures increased homocysteine levels, increased
ask questions about the nature of specific like changing dressings on burns. In oxidative stress, and activated NMDA
drugs and how they work in the body. children – especially so-called difficult glutamate receptors. All of these could
Many of the drugs used in anesthesia pediatric patients – it may be used to contribute to inflammation; additionally,
should be considered relatively safe. For make it easier to start an IV. Ketamine’s nitrous oxide also may cause hematologic
example, Versed® (a benzodiazepine used advantage is that it doesn’t depress problems, neuropathy, and neurotoxic
for sedation, amnesia, and anti-anxiety) respirations like other anesthetics might. effects7.
and fentanyl (a potent narcotic) are It’s also easy to use; it can be given orally, For years, the anesthetic community
relatively short-acting and are not heavily intramuscularly, or intravenously. Typical was told that nitrous oxide was the
metabolized. side effects, however, include open eyes, perfect anesthetic. Now we know better.
Other drugs may present opportunities nystagmus, increased salivation, and A study published in 2003 discussed
to make choices. Propofol, a short-acting emergence delirium. Ketamine alters the the effects of two subsequent nitrous
agent, is administered intravenously patient’s sensory perception, which raises oxide exposures, MTHFR mutation, and
and is used for induction and also for questions about its use for our children the fatal neurological outcome due to a
maintenance of a general anesthetic (i.e., due to the sensory issues many autistic methionine deficiency.8 In 2007, Dr. Victor
keeping the patient asleep). It may be children have. Baum presented a paper at a pediatric
problematic for patients with an allergy Special attention must be paid to the anesthesiology meeting that made us
to soy or eggs; it contains soybean oil use of nitrous oxide. It is one of the oldest all rethink using nitrous oxide as an
and egg phospholipid. Concerns have anesthetics used today and is still used for anesthetic.9
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Methylation is important for “Autism: A brain disorder or a disorder that widely reported in anesthesia journals, and
detoxification, myelin sheath formation, affects the brain?” that clearly lays out Dr. Poling’s conclusions should be easily
neurotransmitters and DNA synthesis. the need to embrace a new paradigm in understood.
How can we help the anesthetic provider understanding autism11. Armed with better information, the
understand that this is one of the In addition, the 2004 article by Dr. S. anesthesia provider should be able to
underlying problems that we see in autism? Jill James and her colleagues, “Metabolic understand the metabolic problems our
How can we help our anesthetic provider biomarkers of increased oxidative stress children have; in many respects, they are
understand that some of our children and impaired methylation capacity in the same problems we see in the increasing
have genetic mutations such as CBS children with autism,” clearly explains the population of chronically ill adults.
(cystathionine beta synthase) and MTHFR, methylation problems in autistic individuals What can you do as parents and
which will affect how they detoxify drugs? that can lead to increased oxidative professionals to help your anesthesia
How can we help the providers understand stress12 . These pathways were considered provider recognize your child’s unique
that our children have increased oxidative in other neurological diseases but never problems? When your child is scheduled to
stress and decreased methylation? How linked to autism before Dr. James’ work. undergo a procedure, consider discussing
can we help them understand that most This article also discusses the use of the following issues during the pre-
of our children have gut problems that B12, folinic acid, and betaine to increase operative conference:
interfere with the absorption of many methylation and reverse the effects of
vitamin co-factors needed for methlylation oxidative stress. This is critical information  Ask not to use nitrous oxide. Most
and detoxification? How do we help them for anesthesia providers. of our kids have a documented B12
realize that many developmentally delayed A recent article from 2008 by Dr. deficiency.
children have some type of mitochondrial Richard Deth, et al. addresses the
dysfunction that may affect the provider’s environmental and genetic factors that  Discuss specific medical and
choice of an anesthetic? How can we help can lead to autism13. The article describes metabolic problems concerning
them understand that many anesthetic a “redox/methylation hypothesis of your child. Tell your provider of any
drugs affect autonomic nervous system autism,” in which oxidative stress, initiated genetic, methylation, detoxification,
function and can have untoward effects by environmental factors in genetically and mitochondrial issues.
in the autistic population? How can we vulnerable individuals, leads to impaired
help them realize that their choices in the methylation and neurological deficits  Consider placement of an IV without
operating room may have detrimental secondary to reductions in the capacity for sedation. Many of our children
effects on our child when they return synchronizing neural networks. This article undergo multiple blood draws and
home? underscores the need to minimize oxidative intravenous treatments. If your
Unfortunately, most anesthesia stress that can result from anesthesia. The child can tolerate an IV placement,
providers have not seen any of the anesthetics that are commonly used may let your anesthesiologist know that
published research discussing biomedical contribute to the toxic load, deplete B12, because the provider usually will
problems in the autistic population. As and affect methylation. not expect children to tolerate this
with other medical disciplines, parents Dr. Jon Poling’s paper published in procedure.
of autistic children have difficulty with 2006 on developmental regression and
the mainstream mindset when we try mitochondrial dysfunction in autism  Inform the anesthesia provider of all
to explain our children’s problems to also helps to explain the overall impact medications, supplements, and IgE
anesthesia providers. We can help educate anesthetic choice may have14 . The allergies.
our anesthetic providers about our mitochondria represent the energy
children’s metabolic problems by referring portion of our cells, and mitochondria are  Make sure the provider understands
them to studies, many of which are listed necessary for the Kreb’s cycle, fatty acid that your child has difficulty
on the Autism Research Institute’s oxidation, metabolism of amino acids, and detoxifying drugs.
Web site10. oxidative phosphorylation. The increased
The best starting point is Dr. Martha risk of certain anesthetics for patients  Ask the provider to keep the
Herbert’s well-reasoned 2005 article titled with mitochondrial problems has been anesthetic as simple as possible.

The most important thing to discuss with the providers  Discuss any other drugs that might
is detoxification pathways. Let them know that your be given in conjunction with the
anesthetics (e.g., acetaminophen,
child may have a problem with glutathione production steroids, and antiemetics).
and have defects in the methlylation pathways. A child’s
liver is not able to detox as much as an adult. The need The most important thing to discuss with
the providers is detoxification pathways.
is to “keep it simple.” Let them know that your child may have a
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BIOMEDICAL
their emotional state – just like anyone else,
and it should be explained to them what is References
going to happen. The receptive language 1
Schure, AY. Difficult pediatric patients:
and intelligence of most autistic children is Anesthetic considerations for children with
much higher than the general public thinks. behavioral problems.” Current Reviews for
Unfortunately, surgery is often necessary, Nurse Anesthetists, Vol. 31 (21) (Feb. 2009).
and that involves an anesthetic to prevent 2
Ibid.
the sympathetic system activation that 3
Kirz, L. Surgical anesthesia and autism.
a pain response elicits. It can be done http://www.autism.com/families/life/kirz.
safely by an informed anesthesia provider. htm.
As with any toxic exposure, we can limit 4
Novak, RJ. Dental anesthesia for the
the harm and increase detoxification autistic child. http://www.autism.com/
pathways to encourage elimination. During families/life/dental.htm.
administration of an anesthetic, the patient 5
Wilder, RT, Flick, RP, Sprung, J, et al.
problem with glutathione production and is given drugs that must be metabolized by Early exposure to anesthesia and learning
have defects in the methlylation pathways. the liver, using various enzymes systems to disabilities in a population-based cohort.
A child’s liver is not able to detox as much convert fat-soluble toxins into water soluble Anesthesiology, April 2005; 110(4): 796-804.
as an adult. The need is to “keep it simple.” substances that can be excreted in the urine 6
Morgan, P. When Propofol is problematic.
Instead of giving three different drugs at or the bile. At home, you can help that Presentation at 12th annual joint winter
the same time for nausea, why not simply process, using the same liver detoxification meeting of the Society of Pediatric
Anesthesia and American Academy of
replace fluids to prevent dehydration, which protocols you may already be using. Pediatrics. http://www.pedsanesthesia.
is the major cause of post-operative nausea. org/meetings/2007winter/pdfs/Morgan-
A mother once asked advice about an  Activated charcoal Friday1130-1150am.pdf.
upcoming procedure because of problems  DMG, TMG, methyl B12, methylfolate 7
See Selzer, RR, Rosenblatt, DS, Laxova, R,
with a prior dental anesthetic. The child Hogan, K. Adverse effect of nitrous oxide in
 Epsom salt baths
was given Versed®, ketamine, Decadron®, a child with 5,10-methylenetetrahydrofolate
nitrous oxide and sevoflurane. The mother  Silymarin (milk thistle) reductase deficiency. New England Journal
complained her son was “out of it” for two  Bentonite clay of Medicine, July 2003; 349: 45–50.
Kalikiri, PC, Sachan Gajraj Singh Sachan, R.
days after the procedure. We discussed the  Antioxidants – vitamins A, C, E Nitrous oxide induced elevation of plasma
questions she should ask her anesthesia  Magnesium homocysteine and methylmalonic acid levels
provider for the next procedure; as a result,  Glutathione and their clinical implications. The Internet
the anesthetic was conducted with just Journal of Anesthesiology, 2004; Vol. 8
Versed® and sevoflurane. The mother used (2). Baum, VC. When nitrous oxide is no
Most anesthesiologists and nurse laughing matter: Nitrous oxide and pediatric
homeopathics at home for the pain and anesthetists want to make the anesthetic anesthesia. Paediatric Anaesthesia, Sept.
swelling. Her child suffered no ill effects experience go as smoothly as possible. 2007; 17(9):824-30.
from the anesthetic. After all, it is their job to make the patient 8
Selzer, et al, supra.
Anesthesia can be done successfully in a feel good.
very simple way. When a neurotypical child
9
Baum, VC, supra.
As an anesthetic provider, I consider
goes to the dentist, does he or she get all it part of my mission to help educate my
10
http://www.autism.com/
of the drugs that many providers seem to colleagues and to help them understand 11
Herbert MR. Autism: A brain disorder or
feel are necessary for our ASD children? that our children are sick – not just autistic. a disorder that affects the brain? Clinical
That is the problem with the way children That is also my mission as a parent, and it is Neuropsychiatry, 2005; 2(6):354-79.
on the spectrum are treated. Too many likewise the mission of all parents. 12
James SJ, et al. Metabolic biomarkers
anesthesia providers are more concerned of increased oxidative stress and impaired
with behavioral issues than they are with methylation capacity in children with autism.
the underlying physical condition. Instead SELECTED COMMON Am J Clin Nutr, Dec. 2004; 80(6):1611-7.
of heavily sedating autistic children, the ANESTHESIA DRUG NAMES 13
Deth, R, Muratore, C, Benzecry J, Power-
providers should consider using fewer Charnitsky, VA, Waly, M. How environmental
drugs, adjusting the dosages to achieve the GENERIC BRAND and genetic factors combine to cause
desired effect. ASD children, in essence, autism: A redox/methylation hypothesis.
fentanyl Sublimaze® Neurotoxicology, Jan. 2008;29(1):190-201.
should be approached in the same manner
that an anesthesia provider approaches halothane Fluothane® 14
Poling, JS, Frye, RE, Shoffner, J,
hepatic- and renal-impaired patients. ketamine Ketalar® Zimmerman, AW. Developmental regression
and mitochondrial dysfunction in a child
In addition to this higher degree of midazolam Versed® with autism. J Child Neurol, Feb. 2006;
respect for their medical condition, our 21(2):170-2.
sevoflurane Ultane®
children should be treated with respect for

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