The Association Between Supra-Physiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients: A Multi-Centre Observational Cohort Study.
Palmer E., Post B., Klapaukh R., Marra G., MacCallum NS., Brealey D., Ercole A., Jones A., Ashworth S., Watkinson P., Beale R., Brett SJ., Young JD., Black C., Rashan A., Martin D., Singer M., Harris S.
RATIONALE: There is conflicting evidence on harm related to exposure to supra-physiologic arterial oxygen tensions (hyperoxemia) in critically ill patients. OBJECTIVES: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to intensive care units (ICUs) in 5 UK University Hospitals. METHODS: Retrospective cohort of ICU admissions between 31st January 2014 - 31st December 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative (CC-HIC). Multivariable logistic regression modelled death in ICU by exposure to hyperoxemia. MEASUREMENTS: Subsets with oxygen exposure windows of 0-1, 0-3, 0-5 and 0-7 days were evaluated, capturing 19,515, 10,525, 6,360 and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mmHg) divided by the hours of potential exposure (24, 72, 120, or 168 hours). MAIN RESULTS: An association was found between exposure to hyperoxemia and ICU mortality [odds ratios (95% compatibility intervals); 1.15 (0.95-1.38), p = 0.15; 1.35 (1.04-1.74), p = 0.02; 1.5 (1.07-2.13), p = 0.02; and 1.74 (1.11-2.72), p = 0.02 for exposure windows of 0-1, 0-3, 0-5 and 0-7 days' duration, respectively. However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation. CONCLUSIONS: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.