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Review
. 2021 Apr;43(4):762-778.
doi: 10.1016/j.clinthera.2021.01.024. Epub 2021 Mar 3.

Anesthesia and the Developing Brain: A Review of Sevoflurane-induced Neurotoxicity in Pediatric Populations

Carol Apai  1 , Rohan Shah  1 , Khoa Tran  2 , Shridevi Pandya Shah  3
Affiliations
Review

Anesthesia and the Developing Brain: A Review of Sevoflurane-induced Neurotoxicity in Pediatric Populations

Carol Apai et al. Clin Ther. 2021 Apr.

Abstract

Purpose: For over 150 years of anesthetic practice, it was believed that the effects of general anesthetics were temporary and not adverse. A growing number of studies over the past 2 decades, however, have identified structural and cognitive abnormalities, especially in the developing brain. Despite the growing evidence of anesthetic-induced neurotoxicity in animal studies, the evidence to date in humans has been inconsistent and unclear. Sevoflurane, a commonly used inhalational agent in pediatric anesthesia, is an agent of choice for inhalational induction due to its rapid activity and low blood-gas solubility. With evaluation of the current literature, improved considerations can be made regarding the widespread use of sevoflurane as an anesthetic.

Methods: PubMed database was searched for article published between 1969 through 2020. The reference lists of identified articles were searched manually for additional papers eligible for inclusion. This review addressed the tolerability of sevoflurane in specific populations, particularly pediatrics, and is divided into 3 parts: (1) the history of sevoflurane use in anesthetic practice and the pharmacokinetic properties that make it advantageous in pediatric populations; (2) proposed mechanisms of anesthesia-induced neurotoxicity; and (3) considerations due to potential adverse effects of sevoflurane in both short and long procedures.

Findings: There is reason for concern regarding the neurotoxic effects of sevoflurane in both the pediatric and elderly populations, as spatial memory loss, developmental deficits, and an enhanced risk for Alzheimer disease have been linked with the use of this popular inhalational agent.

Implications: The duration and dose of sevoflurane may need to be altered, especially in longer procedures in pediatric populations. This may change how sevoflurane is administered, thus indicating a greater demand for an understanding of its limitations as an anesthetic agent.

Keywords: cognitive impairment; memory; neurodevelopment; neurotoxicity; pediatrics; sevoflurane.

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Conflict of interest statement

Disclosures The authors have indicated that they have no conflicts of interest with regard to the content of this article. Authors would like to thank and acknowledge Dr Alex Bekker MD, PhD, Chair, dept of anesthesiology for his support and helpful feedback.