Xenon: An Emerging Neuroprotectant With Potential Application for Cardiac Arrest Care

Xenon is an inert, highly polarizable noble gas with demonstrated safety and application in general anesthesia for over 50 years. A potent inhibitor of the N-methyl-D-aspartate subtype of glutamate receptors, xenon has a well-documented ameliorating effect on excitotoxic neuronal injury in numerous cellular and animal models of hypoxic-ischemic brain injury. The most important determinant of overall survival and morbidity in out-of-hospital cardiac arrest is the severity of neurological injury. The only approved neuroprotective strategy in this setting is mild therapeutic hypothermia, which has demonstrated significant, albeit modest, improvements in mortality. The combination therapy of therapeutic hypothermia and xenon in porcine models of cardiac arrest has shown a greater improvement in functional outcomes than either intervention alone, thereby prompting the study of combination therapy in randomized clinical trials. The treatment of postarrest patients with xenon and mild hypothermia is safe and demonstrates favorable cardiovascular features, including a reduced heart rate, a reduction in troponin elevations, and a decreased need for vasopressors. Combination therapy is superior in protecting white matter integrity than hypothermia alone, but did not significantly impact neurological outcomes at 6-month follow-up. Despite an abundance of preclinical evidence supporting xenon's neuroprotective properties, its translational potential in postcardiac arrest care is indeterminate due to a lack of adequately-powered studies.