Neuronal Cell Death Modalities and Protective Mechanisms Induced By Sevoflurane: A Narrative Review

Sevoflurane is a widely used inhaled anesthetic for adult and pediatric surgeries. In both populations, sevoflurane has been reported to have neurotoxic long-term effects such as cognitive impairment. One of the most important mechanisms for neurotoxicity mediated by sevoflurane is neuronal cell death. In this review, we analyze published data from animal and clinical studies that investigate the potential neurotoxic effects of sevoflurane in both the developing and aged brains. We briefly introduce the characteristics of the major cell death modalities described on exposure to sevoflurane anesthesia (apoptosis, ferroptosis, necroptosis, pyroptosis) as well as mitochondrial dysfunction, oxidative stress, and their involvement in altering neurological functions. We briefly discuss how sevoflurane limits cell death on distinct cells such as cardiomyocytes and under certain conditions such as anesthesia preconditioning. Here, we highlight the importance of distinct cell death modalities in sevoflurane-induced neurotoxicity in populations at risk and propose several strategies for minimizing these effects.