Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, disordered communication skills, and repetitive and restrictive interests which has been rising in diagnostic prevalence and is now estimated to affect up to 1 in 60 children in the United States alone (1). Youth with ASD require health services more frequently than their neurotypical counterparts, and since mutated ASD genes commonly incur a slew of comorbidities, they are met with a growing need for various radiological, surgical, ENT, dental, or diagnostic procedures (2). In these contexts, children with autism are clearly faced with a unique set of challenges – both physiological and behavioral – highlighting the need for awareness and careful anesthesia management of such patients.

Overall, many of the drugs used in anesthesia may be considered relatively safe; for example, both the benzodiazepine Versed and the potent narcotic fentanyl are relatively short-acting and are not heavily metabolized. However, ASD individuals are faced with distinct challenges associated with their unique physiological and pharmacological sensitivities that must be taken into careful consideration when administering anesthesia. 

First, sensory issues inherent to ASD pose a unique challenge. With regard to IV anesthesia, while ketamine can be used to make starting an IV easier, especially in children with ASD, ketamine alters the patient’s sensory perception. In light of ASD sensory hypersensitivities, its use must be limited as such in these children.

Second, allergies – often comorbid with autism – should be assessed when considering anesthetics. For example, propofol, a short-acting agent that is administered intravenously for the induction and maintenance of a general anesthetic, contains soybean oil and egg phospholipid, frequent allergens in individuals with ASD. 

Third, certain unique metabolic and biochemical abnormalities associated with autism should also be considered when selecting an anesthesia drug (3). Propofol may exacerbate mitochondrial disease, which is often comorbid with ASD, for example (4), and should be limited in its use as such. Nitrous oxide might present specific problems for autistic children with common underlying conditions: depleting the B12/folate system and deactivating methionine synthase, it affects all-important methylation functions often dysregulated in children with ASD. Such a deactivation in ASD patients with a defect in the frequently mutated methylenetetrahydrofolate reductase (MTHFR) gene could result in increased homocysteine levels and oxidative stress, and activated NMDA glutamate receptors (5) – exacerbating already dysregulated inflammation in ASD (6,7). Linked to this, problems with detoxification and glutathione production/methylation pathways in ASD individuals must also be considered (8). To this end, simple organic methods are recommended: instead of administering three different drugs at the same time for nausea, simply replacing fluids to prevent dehydration, the major cause of post-operative nausea, should be favored. Homeopathic at-home remedies can also be used for the pain and swelling. 

Finally, in addition to the aforementioned physiological and pharmacological challenges, youth with ASD may exhibit high levels of anxiety when faced with hospital treatment and experience difficulty conforming to the usual pattern of care. Patients with ASD thus need to be met by physicians with sensitive, patient-centric care focused on their emotional and behavioral needs. Preoperatively, most anesthesia providers will and should have a phone interview to discuss ASD children’s needs and ensure individualized, patient-centric planning. Perioperatively, in addition to a greater respect for their medical condition, children with ASD should be treated with respect for their emotional state while using well-adapted forms of communication; this may be achieved by using social stories for psychological preparation and augmentative and assisted communication methods (9). In so doing, strategies such as minimizing wait time, providing quiet areas for pre- and post-operative care, and actively engaging parents are critical (2). 

In conclusion, most anesthesia providers may and should be versed in the guidelines that have been carved out for the successful anesthetic management of patients with ASD to ensure both effective and compassionate pre- and perioperative anesthetic care. 

References

1.            What is Autism Spectrum Disorder? | CDC [Internet]. Available from: https://www.cdc.gov/ncbddd/autism/facts.html

2.            Anesthesia & Autism Spectrum Disorder | Autism Research Institute [Internet]. Available from: https://www.autism.org/anesthesia-and-asd/

3.            Autism: A brain disorder or a disorder that affects the brain? | Request PDF [Internet]. Available from: https://www.researchgate.net/publication/228675792_Autism_A_brain_disorder_or_a_disorder_that_affects_the_brain

4.            Poling JS, Frye RE, Shoffner J, Zimmerman AW. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170–2. 

5.            Methylation/MTHFR and Children with Autism [Internet]. Available from: https://www.theautismexchange.com/organized-information/biomedical/conditions/methylation-mthfr

6.            Selzer RR, Rosenblatt DS, Laxova R, Hogan K. Adverse Effect of Nitrous Oxide in a Child with 5,10-Methylenetetrahydrofolate Reductase Deficiency. N Engl J Med. 2003 Jul 3;349(1):45–50. 

7.            James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004;80(6):1611–7. 

8.            Alabdali A, Al-Ayadhi L, El-Ansary A. A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders. Behav Brain Funct. 2014 Apr 28;10(1):14. 

9.            Short JA, Calder A. Anaesthesia for children with special needs, including autistic spectrum disorder. Contin Educ Anaesth Crit Care Pain. 2013 Aug 1;13(4):107–12. 

10.          Wilder RT, Flick RP, Sprung J, Katusic SK, Barbaresi WJ, Mickelson C, et al. Early Exposure to Anesthesia and Learning Disabilities in a Population-based Birth Cohort. Anesthesiology. 2009.