A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity

Abstract

Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.

Figure 1.

Query and screening process. Our systematic review process included multiple searches of databases and an investigator’s database and a screening process followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews methods. For details, see Supplemental Digital Content, Methods, http://links.lww.com/AA/E704. NLM indicates National Library of Medicine.

Figure 2.

Timeline of brain development for humans and rats. Our systematic review indicated exposure to anesthetics may disrupt key components of brain development. This timeline highlights human developmental milestones,^– and approximate chronological equivalence^– between humans (red) and rats (blue) to aid interpretation of the reports in our systematic review. E indicates rat embryonic day; P, rat postnatal day.