- Atul Malhotra, MD
Atul Malhotra, MD
- Kenneth M Moser Professor, Department of Medicine
- University of California, San Diego
- David R Schwartz, MD
David R Schwartz, MD
- Associate Professor of Clinical Medicine
- Section Chief, Critical Care
- NYU Medical Center
- Richard M Schwartzstein, MD
Richard M Schwartzstein, MD
- Professor of Medicine
- Harvard Medical School
Although supplemental oxygen is valuable in many clinical situations, excessive or inappropriate supplemental oxygen can be deleterious . According to human and animal studies, high concentrations of inspired oxygen can cause a spectrum of lung injury, ranging from mild tracheobronchitis to diffuse alveolar damage (DAD) [2-6]. The latter is histologically indistinguishable from that observed in the acute respiratory distress syndrome (ARDS). The mechanisms and clinical consequences of oxygen toxicity are reviewed here. Specific issues related to the administration of oxygen are discussed separately. (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure" and "Long-term supplemental oxygen therapy".)
Hyperoxia is poorly defined, but probably exists whenever oxygen tension exceeds 21 percent of atmospheric pressure. It appears to produce cellular injury through increased production of reactive oxygen species, such as the superoxide anion, the hydroxyl radical, and hydrogen peroxide [7,8]. When the production of these reactive species increases and/or the cell's antioxidant defenses are depleted, oxygen radicals can react with and impair the function of essential intracellular macromolecules, resulting in cell death .
Oxygen free radicals may also promote a deleterious inflammatory response, leading to secondary tissue damage and/or apoptosis [10-12]. Support for the role of reactive oxygen species in producing cellular injury has come from studies in transgenic mice with altered superoxide dismutase activity. Mice with augmented antioxidant mechanisms have a relative tolerance to hyperoxia, while manganese superoxide dismutase knockout mice die shortly after birth with extensive mitochondrial injury within degenerating neurons and cardiac myocytes [13-15]. Data from animal models suggest possible roles for insulin growth factor 1  and angiopoietin 2  in the pathogenesis of hyperoxia-induced lung injury as well.
Lung tissue is exposed to the highest concentrations of oxygen in the body, placing cells that line the tracheobronchial tree and alveoli at the greatest risk for hyperoxic cytotoxicity . Hyperoxia may also increase susceptibility to mucous plugging, atelectasis, and secondary infection by impairing both mucociliary clearance and the bactericidal capacity of immune cells [19-24].
High fractions of inspired oxygen (FiO2) have been associated with several pulmonary consequences: increased intrapulmonary right-to-left shunt fraction and diminished lung volumes due to absorptive atelectasis; accentuation of hypercapnia; and damage to airways and pulmonary parenchyma. The term "oxygen toxicity" is usually reserved for the last of these consequences, ie, tracheobronchial and pulmonary parenchymal damage.
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