Oxygen Toxicity in Critically Ill Adults

Abstract

Oxygen supplementation is one of the most common interventions in critically ill patients. Despite over a century of data suggesting both beneficial and detrimental effects of supplemental oxygen, optimal arterial oxygenation targets in adult patients remain unclear. Laboratory animal studies have consistently showed that exposure to a high Fi_O2 causes respiratory failure and early death. Human autopsy studies from the 1960s purported to provide histologic evidence of pulmonary oxygen toxicity in the form of diffuse alveolar damage. However, concomitant ventilator-induced lung injury and/or other causes of acute lung injury may explain these findings. Although some observational studies in general populations of critically adults showed higher mortality in association with higher oxygen exposures, this finding has not been consistent. For some specific populations, such as those with cardiac arrest, studies have suggested harm from targeting supraphysiologic Pa_O2 levels. More recently, randomized clinical trials of arterial oxygenation targets in narrower physiologic ranges were conducted in critically ill adult patients. Although two smaller trials came to opposite conclusions, the two largest of these trials showed no differences in clinical outcomes in study groups that received conservative versus liberal oxygen targets, suggesting that either strategy is reasonable. It is possible that some strategies are of benefit in some subpopulations, and this remains an important ongoing area of research. Because of the ubiquity of oxygen supplementation in critically ill adults, even small treatment effects could have a large impact on a global scale.

Keywords: ICUs; hyperoxia; oxygen inhalational therapy.

Figure 1.

The risks of hypoxemia and hyperoxemia and the impact on higher versus lower arterial oxygenation targets for critically ill adults. The Sa_O2 values (x-axis) at which the potential detrimental effects of hypoxemia (blue triangle) or hyperoxemia (orange triangle) occur remain uncertain—and may differ for patients with different acute illnesses and comorbidities. If detrimental effects of hyperoxemia occur only at very high Pa_O2 values and detrimental effects from hypoxemia occur even with modestly low oxygen saturation as measured by pulse oximetry (Sp_O2)/Pa_O2 values, then using a higher Sp_O2 target might improve outcomes (dashed line in upper panel). Conversely, if even modestly supraphysiological Pa_O2 values incur the detrimental effects of hyperoxemia and only severely low Sa_O2/Pa_O2 values incur the detrimental effects of hypoxemia, then using a lower Sp_O2 target might improve outcomes (dashed line in lower panel). Physiologically, patients with impaired oxygen delivery (e.g., anemia) or increased oxygen consumption (e.g., sepsis) might be hypothesized to experience better outcomes with a higher Sp_O2 target (upper panel), whereas patients adapted to chronic hypoxemia (e.g., chronic obstructive pulmonary disease) or certain types of brain injury (e.g., after cardiac arrest) might be hypothesized to experience better outcomes with a lower Sp_O2 target (lower panel).