Oxygen Targets for Mechanically Ventilated Adults with Sepsis: Secondary Analysis of the PILOT Trial

Background: Patients with sepsis frequently require invasive mechanical ventilation. How oxygenation during mechanical ventilation affects clinical outcomes for patients with sepsis remains uncertain. Research Question: To evaluate the effects of different oxygen saturation targets on clinical outcomes for patients with sepsis receiving mechanical ventilation. Study Design and Methods: We performed a secondary analysis of the <u>P</u>ragmatic <u>I</u>nvestigation of optima<u>L</u> <u>O</u>xygen <u>T</u>argets (PILOT) trial dataset among patients who met criteria for sepsis by the Sepsis-3 definition at the time of enrollment. We compared patients randomized to a lower oxygen saturation target (90%; range, 88-92%), an intermediate target (94%; range, 92-96%), and a higher target (98%; range, 96-100%) with regard to the outcomes of 28-day in-hospital mortality and ventilator-free days to study day 28. Results: Of 2541 patients in the PILOT dataset, 805 patients with sepsis were included in the current analysis. In-hospital mortality by day 28 did not differ significantly between the lower target group (48%; 95% confidence interval [CI], 42% to 54%), the intermediate target group (50%; 95% CI, 43% to 56%), and the higher target group (51%; 95% CI, 45% to 56%) (P = 0.83). The number of ventilator-free days to day 28 did not significantly differ between the trial groups, with a mean of 9.9 (standard deviation [SD], 11.8) in the lower oxygen saturation target group, 9.5 (SD, 11.2) in the intermediate group, and 9.4 (SD, 11.4) in the higher group (P = 0.65). Interpretation: Among mechanically ventilated patients with sepsis in a large, randomized trial, the incidence of 28-day in-hospital mortality was not statistically significantly different between the use of a lower, intermediate, or higher oxygen target. However, the confidence intervals included treatment effects that would be clinically meaningfully and further randomized trials of oxygen targets in sepsis are required. Referenced trial name Pragmatic Investigation of optimaL Oxygen Targets Trial (PILOT) ClinicalTrials.gov number NCT03537937URL: https://clinicaltrials.gov/study/NCT03537937.