How to assess the dangers of hyperoxemia: methodological issues

We read with interest the paper by Bellomo and colleagues [1] in the previous issue of Critical Care. We agree with the authors’ fi nal conclusion that there should not be a deliberate policy to decrease the fraction of inspired oxygen (FiO 2 ) in the absence of accurate and reliable oximetry. In the developed world, accurate and reliable oximetry and blood gas results are ubiquitous in ICU settings, the context of their study. However, we have issues with the methods used to come to the conclusion that hyperoxaemia has only a weak relationship with mortality. If one wishes to show no association of hyperoxemia with outcomes, the best approach is to pick the lowest level of arterial partial pressure of oxygen (PaO 2 ). By analogy, if one wished to assess the risk of speeding prior to traffi c accidents, one would not look at the lowest speed or the speed at impact; one would, ideally, look at peak speed or average speed. Kilgannon and colleagues [2] used the fi rst blood gas measurement in the ICU and found that hyperoxemia (PaO 2 of at least 300 mm Hg) was associated with increased risk of death in the hospital. de Jonge and colleagues [3] looked at mean PaO 2 of mechanically ventilated patients in the fi rst 24 hours in ICUs and also reported an increased risk of death in patients with hyperoxemia. We are also concerned that the conclusion of the study relates to hyperoxemia when defi ned as a PaO 2 of greater than 400 mm Hg whereas the study objective was to analyze the risk of death if the PaO 2 was at least 300 mm Hg. We understand that the authors did fi nd excess mortality in their intended study group (and in those with a PaO 2 of greater than 200 mm Hg) even after adjust ment for illness severity. We are concerned that their negative conclusion is based on a diff erent (and smaller) post hoc subset of patients with a PaO 2 of greater than 400 mm Hg. By contrast, Kilgannon and colleagues [4] re-analyzed their data and reported a clear dose response with lowest hospital mortality in the PaO 2 range of 60 to 99 mm Hg and they reported a 24% increase in mortality risk for every 100 mm Hg increase in PaO 2 .