Pulmonary Oxygen Toxicity

doi:10.1378/chest.88.6.900

Chest

Volume 88, Issue 6, December 1985, Pages 900-905

https://doi.org/10.1378/chest.88.6.900 Get rights and content

Although oxygen therapy has been used in the care of critically ill patients for many years, the recognition of pulmonary oxygen toxicity as an important clinical problem is relatively recent. The biochemical basis of oxygen toxicity is increased production of highly reactive, partially reduced metabolites of oxygen, including hydrogen peroxide and free radicals, by cells in hyperoxia. Enzymatic intracellular defense mechanisms exist which protect cells from the toxic effects of oxygen free radicals. The physiologic manifestations of oxygen toxicity include decreases in vital capacity, diffusing capacity, and lung compliance. The pathologic changes of oxygen toxicity are not specific and resemble those of the adult respiratory distress syndrome. Many drugs used in the care of patients, including bleomycin, nitrofurantoin, and corticosteroids, may exacerbate oxygen-induced lung injury. No effective pharmacologic means exist for lessening pulmonary oxygen toxicity in humans.

Section snippets

The Biochemical Basis of Oxygen Toxicity

During normal cellular respiration partially reduced and thus highly reactive oxygen metabolites are produced. These chemical species are referred to as free radicals; by definition they have an unpaired orbital electron. They may act chemically as either reductants or oxidants.⁶ Most of the molecular oxygen used for respiration in cells is reduced directly to water with the sequential addition of four electrons by mitochondrial cytochrome oxidase. A small fraction of oxygen used metabolically

Clinical Manifestations

The rate at which oxygen toxicity develops is directly related to the partial pressure of inspired oxygen. No toxicity is ordinarily detectable when the concentration of inspired oxygen is less than 50 percent.² However, most data regarding the tolerable limits of oxygen breathing have been obtained from normal, healthy young subjects—not patients with cardiopulmonary diseases. Thus, the effects of underlying disease on the development of oxygen toxicity are largely unknown.

In conscious

Pathologic Manifestations

Comprehensive structural studies of pulmonary oxygen toxicity, including ultrastructural morphometry, have been done in experimental animals. Only a few studies have been performed in human subjects; typically, these have been patients at autopsy after severe illnesses which required high concentrations of oxygen (usually delivered through mechanical ventilators) for long periods. Consequently, while the details and time course of pulmonary oxygen toxicity are well known in experimental

Pharmacologic Alteration of O₂ Toxicity and Development of O₂ Tolerance

The effects of many different compounds on the rate of development and severity of oxygen toxicity in experimental models have been reviewed.2, 48 Some commonly used drugs exacerbate oxygen toxicity in experimental animals, and may have similar effects in humans. For example, dexamethasone(0.4mg/kg/day) treatment of rats in hyperoxia results in both greater oxygen-induced lung injury and lower activities of the lung's antioxidant enzymes.⁴⁹ This is of potential (but unproved) importance since

Conclusion

While oxygen therapy has been used for many years, the existence of pulmonary oxygen toxicity as a problem in clinical medicine has been widely recognized only within the last 20 years. The formation of oxygen free radicals during cellular metabolism in hyperoxia is now recognized as a biochemical basis of oxygen-induced injury to cells and organs. The importance of adaptive changes including proliferation of oxidant-resistant alveolar lining cells and increases in intracellular antioxidants

Acknowledgment

The author thanks Dr. J. Pisarello for his help in preparation of this essay.

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: Supported by research grants from the Veterans Administration Research Service and the American Lung Association.

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