The dilemma of hyperoxia following positive pressure mechanical ventilation: role of iron and the benefit of iron chelation with deferasirox

Abstract

Background and Objective: Increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia) is considered to be one of the major mechanisms of lung injury, which is thought among different mediators, transition metal ion, iron, by generation of very reactive free radicals which play an important role. Disruption of normal iron homeostasis has been reported in hyperoxic conditions. We hypothesized that chelation of iron can reduce hyperoxia-induced lung injury. Methods: Mechanically ventilated patients, who received oxygen with FiO(2) > 0.5 for at least 3 days, underwent bronchoscopy before and 72 hours after receiving "Deferasirox". Oxidative injury index and iron homeostasis markers were measured in lavage fluid and plasma. Results: In 12 patients, the concentrations of 8-isoprostane (p = 0.005), 8-oxoguanine (p = 0.04), carbonyl proteins (p = 0.04) - as markers of oxidative stress - decreased significantly in lavage fluid after intervention. Levels of iron-related proteins, ferritin (p = 0.04) and transferrin (p = 0.005) also decreased significantly in lavage fluid. Conclusion: Deferasirox - as an iron chelator - decrease oxidative injury index in hyperoxic condition and it could be consider safe and beneficial agent, along with other supportive measures in hyperoxia-induced lung injury for better toleration of oxygen therapy.