Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial

Abstract

<b>Rationale:</b> Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. <b>Objectives:</b> This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. <b>Methods:</b> This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (Pa_O₂, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (Pa_O₂, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. <b>Measurements and Main Results:</b> Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved Pa_O₂ was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; <i>P</i> = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. <b>Conclusions:</b> Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).