Xenon as a Neuroprotective Agent in Surgical Anesthesia: A Systematic Review

Abstract

Xenon, a noble gas anesthetic, has been studied for its potential neuroprotective effects during surgical anesthesia. This systematic review synthesizes findings from 30 clinical, preclinical, and mechanistic studies evaluating xenon’s role in preventing postoperative neurocognitive disorders (PNDs), including delirium and cognitive dysfunction. Clinical evidence from randomized trials and meta-analyses (≈3,200 patients) shows that xenon improves hemodynamic stability, reduces vasopressor requirements, and accelerates emergence from anesthesia, but does not consistently lower PND incidence or enhance postoperative cognitive performance. In contrast, preclinical studies across models of traumatic brain injury, ischemia, seizures, stroke, and Alzheimer’s disease demonstrate robust neuroprotection, with reduced neuronal loss, apoptosis, oxidative stress, and cognitive deficits, as well as restoration of synaptic plasticity. Mechanistic insights highlight xenon’s antagonism of NMDA and HCN2 channels, modulation of oxidative and inflammatory pathways, and synaptic preservation, with innovative delivery strategies (e.g., nanobubbles) enhancing efficacy. Despite compelling preclinical results and perioperative benefits in humans, xenon’s clinical neuroprotective effects remain inconclusive, partly due to heterogeneous patient populations and methodological limitations. High cost and limited availability further restrict its widespread use. Future large-scale, standardized trials and advanced delivery approaches are needed to clarify xenon’s therapeutic role and bridge the translational gap between experimental promise and clinical practice.