Xenon Combined With Hypothermia in Perinatal Hypoxic-Ischemic Encephalopathy: A Noble Gas, a Noble Mission

Perinatal hypoxia-ischemia is a major cause of neonatal morbidity. It generates primary neuronal damage of the neonatal brain and later secondary damage when reperfusion of the ischemic brain tissue causes a surge of oxygen free radicals and inflammation. This post-hypoxic-ischemic brain damage is a leading cause of motor and intellectual disabilities in survivors. Research worldwide has focused on mitigating this injury. Mild or moderate hypothermia is the standard treatment in many centers. However, its benefit is modest and the search for combinatorial effective neuroprotectants continues. This review focuses on xenon as one such agent. The use of mild to moderate hypothermia is reviewed first. Then promising results on the use of xenon to potentiate the effect of hypothermia in in vitro and in vivo animal experiments are discussed. In the first feasibility study on human neonates, researchers found a significant benefit of using 50% xenon for 18 hours in addition to 72 hours of hypothermia. Yet, this additional benefit of xenon was lacking in a larger cohort study, potentially because xenon was used beyond six hours of birth. The future of using xenon is promising, but further clinical studies are awaited to confirm the feasibility of its routine use and its optimal timing, concentration, and duration, for human neonatal hypoxia-ischemia.