EC: Anesthetic Neurotoxicity

Provocative & Possibly Problematic

The Issue & Concern:

The medical profession is currently concerned about the possibility of anesthetic neurotoxicity in children who are exposed to anesthetic agents at an early age (less than 3 years old). Animal data from anesthesia research literature has shown that anesthetic agents may cause potential harm to young, developing neurologic systems. Even though young mammalian animals are very different from human babies and children, the possibility of potential anesthetic neurotoxicity is of genuine concern.

A few points to consider:

  • Children require surgical procedures that are not elective (trauma, infection, tumors, etc).
  • Most young children require general anesthesia to carry out necessary surgical procedures.
  • Not performing the indicated surgical procedure(s) or delaying the procedures until they are older may lead to significant developmental delays themselves.
  • There are many variables that must be considered:
    • Types of anesthetic agents
    • Number of anesthesias at various ages
    • Age, year and quartile of birth
    • Maternal age at birth and socioeconomic level
    • Gestational age
    • Rurality of the mother's residence
    • Gender
    • Nature of the illness being treated
    • Associated and non-associated co-morbidities
    • Age range to study and continued longitudinal data as the child ages
    • Validity of the assessment tests used to determine developmental status
    • Method of statistical analysis, method of studying cohorts and cohort matching, etc.
    • Unknown pre-existing neurologic conditions
    • Genetic issues and factors
    • Other unknown factors

At this time, medicine does not know the answers to the many questions related to this topic. However, very thoughtful physicians and researchers are asking the right questions and are seeking some answers. The answers will help to establish current and future guidelines.

Children of all ages require surgical interventions to treat serious medical problems as well as to prevent serious medical problems, and require anesthetic agents in order for those procedures to be performed safely and properly.

  • Non-elective procedures should be performed in a timely manner to decrease exposure time.
  • Exposure to the fewest anesthetic procedures and agents as possible should be the goal
  • Combining several surgical procedures during one anesthesia exposure should be considered, if it is safe for the child


Research studies are ongoing concerning this topic. The issue is provocative and problematic. We need more studies on humans and need to be very cognizant of the current dilemma.

Two recent studies with very large groups of children, O'Leary et al. (Canada) and Glatz et al. (Sweden), have shown no statistically significant affect of pediatric anesthesia on children younger than 4 years in terms of any long term cognitive impairments. Both studies had large "N's" and school testing data.

A recent study published by Block etal. from The University of Iowa has examined whole brain white matter volume and white matter integrity and found lower volumes and integrity for exposed versus unexposed children. However, only 17 exposed male and 17 unexposed male patients were evaluated and all patients except one were caucasians. Selection bias was present in the study. And, there was no correlation with any cognitve testing of the subject. Did the volumetric and integrity differences lead to any learning issues? More data is needed.

Such reports are very important as we continue to study and evaluate the issue. I have provided references below if you are interested in reading some of the more important studies.

FDA Drug Safety Communication:

The U.S. FDA published an FDA Drug Safety Communication on December 14, 2016. The reference and link to the FDA is provided below if you would like to learn more.




1. Wilder RT, et al. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology 2009 April ; 110(4): 796–804. Click here for a .pdf copy.

2. Rapport BA, et al. Anesthetic neurotoxicity - Clinical implications of animal models. NEJM, Feb 26, 2015, 372:9:796-797. Click here for a .pdf copy.

3. O'Leary JD, et al. A population-based study evaluating the association between surgery in early life and child development at primary school entry. Anesthesiology 2016, 125;2:272-278. Click here for a .pdf copy.

4. Glatz P, MD; Sandin RH, Pedersen NL, Bonamy AK, Eriksson LI, Granath F. Association of Anesthesia and Surgery During Childhood With Long-term Academic Performance. JAMA Pediatr. doi:10.1001/jamapediatrics.2016.3470
Published online November 7, 2016. Click here for a .pdf copy.

5. Andropoulos DB, Greene MF. Anesthesia and developing brains - implications of the FDA warning. N Engl J Med, March 9, 2017, 376;10:905-907. Click here for a .pdf copy.

6. FDA Drug Safety Communication, 12-14-16. Click here for a .pdf copy. Click here to access the FDA web site and additional information.

7. Janik LS. The effect of general anesthesia on the developing brain: appreciating parent concerns while allaying their fears. APSF Newsletter, October 2016, 38-39. Click here for a .pdf copy.

8. Grover LA, Mitchell RB, Szmuk P. Anesthesia exposure and neurotoxicity in children - understanding the FDA warning and implications for the otolaryngologist. JAMA Otolaryngol Head Neck Surg 2017;143(11):1071-1072. Click here for a .pdf copy.

9. Block RI, Magnotta VA, Bayman EO, Choi JY, Thomas JJ, Kimble KK. Are anesthesia and surgery during infancy associated with decreased white matter integrity and volume during childhood? Anesthesiology 2017:127:788-797. Click here for a .pdf copy.

Updated January 19, 2018