Gas as medicine: the case for hydrogen gas as a therapeutic agent for critical illness

Abstract Molecular hydrogen gas (HG), administered through inhalation or as hydrogen-rich fluids (HRF), has demonstrated antioxidant, anti-inflammatory, antiapoptotic, cytoprotective, and beneficial mitochondrial effects in critical illness. Preclinical studies and human clinical studies consistently endorse hydrogen gas as safe, with mechanisms of action linked to vital molecular pathways, such as reductions in both oxidative stress and inflammation with beneficial effects on mitochondria. In preclinical studies, HG has been shown to improve outcomes in conditions such as sepsis, acute lung injury, hepatic injury, pancreatitis, cardiac arrest, traumatic injury, acute kidney injury, and brain injury. HG has been given to human subjects across multiple disease states and has a good safety profile with encouraging clinical effects. Given its accessibility, safety, and low-cost, hydrogen gas therapy should be assessed in adequately powered clinical trials in critical illness.