This scoping review sought 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. Using a search focused on sevoflurane, propofol, and dexmedetomidine as representative agents, their explorations were constructed using a modified Patient Intervention, Comparison, Outcome (PICO) framework. The summary of evidence and major findings suggest that exposure to anesthesia disrupts molecular and cellular pathways in brain development, alters animal behavior, and might impair human neurodevelopmental outcomes. The included studies shared no obvious single common cellular or molecular mechanism for toxicity, which accounts for the diversity of reported findings. The authors summarize that the strongest evidence for neurotoxic effects in humans is from multiple exposures, most likely in the domains of attention and disruptive behaviors, and possibly executive functioning, memory, motor skills, and language abilities.
Matthew Thomas Borzage, PhD, and Bradley S. Peterson, MD
Anesthesia & Analgesia February 2025