Pulmonary oxygen toxicity. A review of the evidence for acute and chronic oxygen toxicity in man.

During the last few years there has been growing concern that chronic pulmonary oxygen toxicity might result from the administration of high concentrations of oxygen with intermittent positive pressure ventilation (IPPV) during the management of respiratory failure. This concern was fostered by Nash, Blennerhassett and Pontoppidan (1967) who reported an association between the duration and concentration of oxygen administered to patients receiving IPPV, and the appearance of a series of pathological changes characterized by an early exudative phase and a late proUferative phase. Northway, Rosan and Porter (1967) observed in neonates with hyaline membrane disease, who had received IPPV and oxygen, a prolongation of the healing phase and the appearance of an apparently new chronic pulmonary syndrome. They associated this syndrome with IPPV and the administration of high concentrations of oxygen. Although these studies have provided evidence of an association between the prolonged administration of oxygen and the functional and pathological features which have been described, they do not provide evidence of a cause-and-effect relationship. Moreover, as illustrated by the papers of Brewis (1969), and Soloway, Castillo and Martin (1968) there has been a tendency to attribute functional, radiological and histological changes to oxygen toxicity without a consideration of other possible mechanisms for these changes. In addition to the possible direct toxicity of oxygen on alveolar cells, capillaries, and the surface lining of alveoli, there are several other distinctly different mechanisms whereby high concentrations of oxygen could alter pulmonary function. These include the rapid absorption of gas in the absence of nitrogen if airway closure or obstruction is present (Dale and Rahn, 1952; Rahn and Farhi, 1963); impairment of mucociliary transport (Laurenzi, Yin and Guarneri, 1968; Marin and Morrow, 1969); and the indirect effect of high partial pressures of oxygen on the control of ventilation and the adequacy of gas exchanges when the ventilatory response to carbon dioxide is impaired. The primary purpose of this review is to examine the evidence for pulmonary oxygen toxicity in man, when oxygen is administered at normobaric conditions or the equivalent partial pressure. However, because of the obvious limits to experimental evidence in man the effects of prolonged administration of high concentrations of oxygen in experimental animals and primates will also be discussed, where this is relevant to the evaluation of the evidence of pulmonary oxygen toxicity in man.