Original Investigation Caring for the Critically Ill Patient

Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients: A Randomized Clinical Trial

Harry Gelissen, Harm-Jan de Grooth, Yvo Smulders, et al

JAMA. Published online August 31, 2021. doi:10.1001/jama.2021.13011

Abstract

Importance  Hyperoxemia may increase organ dysfunction in critically ill patients, but optimal oxygenation targets are unknown.

Objective  To determine whether a low-normal Pao₂ target compared with a high-normal target reduces organ dysfunction in critically ill patients with systemic inflammatory response syndrome (SIRS).

Design, Setting, and Participants  Multicenter randomized clinical trial in 4 intensive care units in the Netherlands. Enrollment was from February 2015 to October 2018, with end of follow-up to January 2019, and included adult patients admitted with 2 or more SIRS criteria and expected stay of longer than 48 hours. A total of 9925 patients were screened for eligibility, of whom 574 fulfilled the enrollment criteria and were randomized.

Interventions  Target Pao₂ ranges were 8 to 12 kPa (low-normal, n = 205) and 14 to 18 kPa (high-normal, n = 195). An inspired oxygen fraction greater than 0.60 was applied only when clinically indicated.

Main Outcomes and Measures  Primary end point was SOFA_RANK, a ranked outcome of nonrespiratory organ failure quantified by the nonrespiratory components of the Sequential Organ Failure Assessment (SOFA) score, summed over the first 14 study days. Participants were ranked from fastest organ failure improvement (lowest scores) to worsening organ failure or death (highest scores). Secondary end points were duration of mechanical ventilation, in-hospital mortality, and hypoxemic measurements.

Results  Among the 574 patients who were randomized, 400 (70%) were enrolled within 24 hours (median age, 68 years; 140 women [35%]), all of whom completed the trial. The median Pao₂ difference between the groups was −1.93 kPa (95% CI, −2.12 to −1.74; P < .001). The median SOFA_RANK score was −35 points in the low-normal Pao₂ group vs −40 in the high-normal Pao₂ group (median difference, 10 [95% CI, 0 to 21]; P = .06). There was no significant difference in median duration of mechanical ventilation (3.4 vs 3.1 days; median difference, −0.15 [95% CI, −0.88 to 0.47]; P = .59) and in-hospital mortality (32% vs 31%; odds ratio, 1.04 [95% CI, 0.67 to 1.63]; P = .91). Mild hypoxemic measurements occurred more often in the low-normal group (1.9% vs 1.2%; median difference, 0.73 [95% CI, 0.30 to 1.20]; P < .001). Acute kidney failure developed in 20 patients (10%) in the low-normal Pao₂ group and 21 patients (11%) in the high-normal Pao₂ group, and acute myocardial infarction in 6 patients (2.9%) in the low-normal Pao₂ group and 7 patients (3.6%) in the high-normal Pao₂group.

Conclusions and Relevance  Among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal Pao₂ target compared with a high-normal Pao₂ target did not result in a statistically significant reduction in organ dysfunction. However, the study may have had limited power to detect a smaller treatment effect than was hypothesized.

Trial Registration  ClinicalTrials.gov Identifier: NCT02321072