Chapter 45. Oxygen Toxicity

The importance of the physiology and toxicology of oxygen (O2) breathing have increased in recent years. The past 25 years have witnessed a remarkable upsurge of knowledge and interest in “oxidative stress” throughout all of biology. The use of O2 continues to grow, from critically ill to ambulatory patients and even to recreational use at “oxygen bars.”1 Recent advances in patient care have refocused attention on the optimum use of O2. For example, currently, strategies to protect the lung from mechanical injury during mechanical ventilation emphasize the use of lower tidal volumes. But such strategies may impair gas exchange, resulting in higher requirements for inspired O2 fraction (FIO2).2

Lavoisier initially characterized O2 as “highly respirable air”3 and “vital air” before eventually giving it the name “principle oxygine” (acidifying principle) in 1777. He took the name from the Greek roots “oxy” (acid) and “gen” (to form), because initially O2 was incorrectly believed to be the essential principle in the formation of acids.4 Normobaric hyperoxia may be defined as an inspired O2 tension,

J.B.S. Haldane5 and others6 speculated, and it is now generally accepted, that life on earth began anaerobically when the earth’s atmosphere was virtually devoid of O2. Gilbert6 postulated that in this primordial reducing atmosphere, the first living cells used hydrogen, diffusing into the cell from the environment, as an energy source (e.g., metabolizing carbohydrates to methane and water). Gilbert6 speculated further that because hydrogen would also reduce essential cellular constituents and thereby poison the cell, these early cells also had to develop antihydrogen defenses and actively transport hydrogen ions out of the cell. As the atmosphere was transformed from a reducing to an oxidizing one, O2 replaced hydrogen as an energy source. Therefore, to avoid O2 poisoning, cells then had to develop antioxygen and antioxidant defenses. These observations emphasize that as an energy source for cells, O2 has a dual effect: It is both life promoting and life destroying. This dual nature of O2 (Fig. 45-1) was noted by Priestley in 1775 shortly after his discovery of O2: “though pure [oxygen] might be very useful as a medicine, … as a candle burns out much faster in [oxygen] … so we might … live out too fast.”7 Indeed, even at ambient concentrations, O2 is now considered to play a role in the natural process of aging.8–10 In 1777, Scheele, who independently discovered O2, noted along with Priestley that O2 is toxic to plants. In 1785, Lavoisier, who first recognized the vital role of O2 in the equivalent processes of respiration and combustion, commented explicitly ...