Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients

Abstract

IMPORTANCE Hyperoxemia may increase organ dysfunction in critically ill patients, but optimal oxygenation targets are unknown.OBJECTIVE To determine whether a low-normal PaO 2 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 PaO 2 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 PaO 2 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 PaO 2 group vs −40 in the high-normal PaO 2 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 PaO 2 group and 21 patients (11%) in the high-normal PaO 2 group, and acute myocardial infarction in 6 patients (2.9%) in the low-normal PaO 2 group and 7 patients (3.6%) in the high-normal PaO 2 group.CONCLUSIONS AND RELEVANCE Among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal PaO 2 target compared with a high-normal PaO 2 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.

Dangers of hyperoxia

“…Indeed, based on the distribution of data, there is a 46% chance that conservative O 2 therapy increases absolute mortality by more than 1.5% points, and a 19% chance that conservative O 2 therapy decreases absolute mortality by more than 1.5% points [ 41 , 42 ]. Finally, a recent RCT conducted in ICU patients fulfilling the systemic inflammatory response syndrome criteria, found no significant difference between high-normal and low-normal oxygenation targets for non-respiratory organ dysfunction over the first 14 days, or in Day-90 mortality [ 43 ]. Accordingly, the most appropriate dose of O 2 to give to adult ICU patients remains uncertain.…”

Association of Arterial Hyperoxia With Outcomes in Critically Ill Children

“…On this note, there have been several trials comparing liberal vs restrictive oxygen targets over the past years in critically ill adults. 44 , 57 , 58 , 59 , 60 Although a meta-analysis of the earliest trials supported an increased risk for mortality on use of liberal oxygen targets, 57 these findings were disputed by a recent updated meta-analysis including more large-scale trials. 58 The most recent trials also did not find a clear harmful effect of liberal oxygenation on outcomes, 44 , 59 , 60 which suggests that the true effect size of hyperoxia is probably much smaller than previously suggested from observational studies and more complex than thought.…”

Hyperoxemia in postsurgical sepsis/septic shock patients is associated with reduced mortality

“…In addition, the LOCO-2 study conducted in ARDS patients did not report differences in mortality at 28 days when using a conservative oxygenation therapy (PaO 2 55–70 mmHg; SpO 2 of 88 to 92%) vs. liberal oxygen therapy (PaO 2 90–105 mmHg; SpO 2 ≥ 96%) [ 47 ]. Gelissen et al [ 48 ] reported that among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal PaO 2 target (PaO 2 range of 60–90 mmHg) compared with a high-normal PaO 2 target (PaO 2 range of 105–135 mmHg) did not result in a reduction in organ dysfunction. Zhang et al [ 49 ] reported that the effect of PaO 2 on mortality risk is a quadratic function in sepsis, in which both low and high PaO 2 were associated with a high mortality risk.…”