Greater numbers of severe hyperoxemia events appeared to be associated with increased mortality in this large, diverse cohort of critically ill children, supporting a possible exposure-response association between severe hyperoxemia and outcome in this population.

Although further prospective evaluation appears to be warranted, this study’s findings suggest that guidelines for ongoing management of critically ill children should take into consideration the possible detrimental effects of severe hyperoxemia.

Of 23,719 PICU encounters during the inclusion period, 6,250 patients had at least 1 measured Pao2 value.

Severe hyperoxemia was independently associated with in-hospital mortality.

The highest Pao2 values during hospitalization were dichotomized according to the definition of severe hyperoxemia and assessed for association with in-hospital mortality using logistic regression models incorporating a calibrated measure of multiple organ dysfunction, extracorporeal life support, and the total number of arterial blood gas measurements obtained during an encounter.

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