Oxygen toxicity and tolerance

Normobaric oxygen toxicity is well described in all animal species. However susceptibility to oxygen exposure is highly variable according to age, species and strains. Similarly in humans, prolonged high oxygen exposure is reported to induce cough, shortness of breath, decrease vital capacity and increase alveolo-capillary permeability. The toxic FIO2 threshold (length of exposure and level) is still debated. In patients with previous lung injury, this threshold is even more difficult to delineate as pathologic pulmonary lesions might result from hyperoxia or primary lung insult. Oxygen free-radicals play a key role in the pathophysiology of oxygen toxicity. Oxygen resistance or tolerance is obtained with intraperitoneal, intravenous and intratracheal endotoxin or cytokines administration. Previous exposure to high oxygen concentration is also reported to increase survival rate and decrease pulmonary lesions in animal models. Protection may rely on antioxidant enzymes synthesis, nitric oxide production, neutrophils recruitment and modulation of alveolar macrophages activity. In humans, oxygen tolerance might be suspected through several clinical studies reporting favorable outcome after long term-oxygen exposure. Better knowledge of the risks of prolonged high oxygen exposure is important to re-evaluate the goals of mechanical ventilation (FIO2, SaO2, PEEP) and/or to develop treatments to prevent oxygen toxicity (surfactant, antioxidant enzymes).