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biomedical Risk of Anesthesia Regression in …

biomedical Risk of Anesthesia Regression in Children with Autism Spectrum Disorder and Mitochondrial Dysfunction By Gail Szakacs, MD and Alyssa Davi C. Gail Szakacs, hildren with autism spectrum disorder and suggests tools to help prevent adverse MD, is a (ASD) have a range of medical problems events from Anesthesia in ASD children with board-certified internist. involving many organ systems. A subset mitochondrial dysfunction. The information Since 2006, of children with ASD hasve abnormal in this article is meant to increase awareness Dr. Szakacs has mitochondrial energy production and function about an evolving concern for a very vulnerable been involved that contributes to their physical, cognitive, population and should be applied to an with Defeat Autism Now!

Gail Szakacs, MD, is a board-certified internist. Since 2006, Dr. Szakacs has been involved with Defeat Autism Now! ® and dedicated her medical practice

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1 biomedical Risk of Anesthesia Regression in Children with Autism Spectrum Disorder and Mitochondrial Dysfunction By Gail Szakacs, MD and Alyssa Davi C. Gail Szakacs, hildren with autism spectrum disorder and suggests tools to help prevent adverse MD, is a (ASD) have a range of medical problems events from Anesthesia in ASD children with board-certified internist. involving many organ systems. A subset mitochondrial dysfunction. The information Since 2006, of children with ASD hasve abnormal in this article is meant to increase awareness Dr. Szakacs has mitochondrial energy production and function about an evolving concern for a very vulnerable been involved that contributes to their physical, cognitive, population and should be applied to an with Defeat Autism Now!

2 And behavioral impairments. The presence of individual patient under the guidance of the and dedicated her medical practice mitochondrial dysfunction increases the risk doctors involved in the child's care. to the care of those with autism for potential damage to the brain, which is spectrum disorder and other special dependent on oxidative metabolism. This risk What does some of the research say needs and chronic illnesses. She and Dr. Nancy O'Hara have an integrative is more pronounced during procedures that about mitochondrial disease in ASD and medicine practice in Connecticut.

3 Dr. require Anesthesia . Because ASD children often increased anesthetic sensitivity with Szakacs mentors clinicians around undergo medical procedures (like endoscopies, mitochondrial disease? the world, teaching a comprehensive adenoidectomies, tonsillectomies, and ear tube Emerging research suggests that a percentage and integrative approach to treating ASD and chronic illness. placement) requiring Anesthesia , Regression of ASD children actually have underlying with Anesthesia is of particular concern for the mitochondrial disease, specifically defects Alyssa Davi subset of children with ASD and mitochondrial in mitochondrial oxidative phosphorylation is a former dysfunction.

4 (OXPHOS). Oliveira and colleagues published a special education This article introduces aspects of emerging population-based survey of school-age children teacher and research, highlights potential risk factors, with ASD in which they found that 7% of is involved the nonprofit organization Parents Ending America's Childhood The presence of mitochondrial dysfunction increases the risk for Epidemic (PEACE), which is sponsoring the parent outreach potential damage to the brain, which is dependent on oxidative project Epidemic Answers. Please metabolism. This risk is more pronounced during procedures visit or you can contact Alyssa at Alyssa@ that require Anesthesia .

5 Because ASD children often undergo medical procedures (like endoscopies, adenoidectomies, tonsillectomies, and ear tube placement) requiring Anesthesia , Regression with Anesthesia is of particular concern for the subset of children with ASD and mitochondrial dysfunction. biomedical . those who were fully tested met criteria What are some of the risk factors What complications can be seen in for definite mitochondrial respiratory for Anesthesia complications? ASD children with mitochondrial chain disorders and were also clinically Since ASD children commonly have one or dysfunction following Anesthesia ?

6 Indistinguishable from other children more of the following underlying medical Anesthesia and sedation do not present with ASD. Weissman, et al. published a problems, they are often at increased a problem for most children with ASD. comprehensive chart review of 25 ASD risk for complications from procedures However, ASD children with mitochondrial patients with a mitochondrial disorder requiring Anesthesia . disturbances are at increased risk for the in which they showed a non-chance following potential complications: occurrence of these two disorders. 1. History of seizures Other research about specific 2.

7 Preoperative respiratory problems 1. Excessive timeframe or difficulty in mitochondrial abnormalities and increased 3. Poor clinical condition prior to the coming out of the Anesthesia . anesthetic sensitivity may provide insight procedure 2. Developmental regressions, which into how to better identify those at higher 4. Undiagnosed mitochondrial could include loss of expressive and/. risk for anesthetic complications in the disease or receptive language, gross motor future. The background of this research is 5. MTHFR (methylenetetrahydrofolate skills, fine motor skills, cognitive explained here, in addition to the actual reductase) gene polymorphism function, and overall neurologic research, to highlight its importance.

8 6. Increased homocysteine levels deterioration. In some children, skill Mitochondria are the main source of 7. General B-vitamin complex loss may be permanent. cellular energy metabolism, and the central deficiency or B12 deficiency 3. Excessive fatigue and reduced nervous and muscular systems have a very (indicated by increased energy levels: temporary (for days or high energy demand. As the targets of methylmalonic acid) as the cause of weeks) or persistent. Anesthesia , these systems are particularly increased homocysteine levels 4. Possible death. vulnerable in the presence of mitochondrial dysfunction.

9 The mitochondrial oxidative The following table is from a 1998 article, Anesthesia and Mitochondrial Cytopathies, . phosphorylation pathway consists of five by Bruce H. Cohen, et al. It illustrates the mechanism for the effects of certain anesthetic protein complexes (I-V), and complex I is agents on mitochondrial function and may at least partially explain the occurrence of the entry point for this pathway in normal adverse events noted above. mitochondria. Therefore, problems in complex I may more significantly and negatively affect overall functional capacity Medication Biochemical and Clinical Effects on in the central nervous and other systems.

10 Mitochondrial Function Subcomplex I lambda is part of complex I. Barbiturates Inhibits complex I activity at high levels Along with other researchers, Marni J. Falk, MD (assistant professor of pediatrics, Benzodiazepines Inhibits adenosine nucleotide translocase Division of Human Genetics at The Children's Hospital of Philadelphia), has Propofol and/or lipid carrier Inhibits mitochondrial function studied certain aspects of complex Halothane Increased risk for heart rhythm disturbances I mitochondrial dysfunction. They conclude subcomplex I lambda subunits Nitrous oxide (chemical Neurotoxic, possibly by increasing nitric oxide along the electron transport pathway formula is N2O) production, which inhibits cis-acotinase and specifically control whole animal anesthetic iron-containing electron transport enzymes.


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