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 Pragmatic Investigation of optimaL Oxygen Targets (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.