No clear benefit of intensive oxygen therapy in ICU patients: NEJM
Australia: The use of conservative oxygen therapy versus usual oxygen therapy made no significant impact on the number of ventilator-free days in patients undergoing mechanical ventilation in the ICU (intensive care unit), according to a recent study presented at the World Congress of Intensive Care in Melbourne, Australia. The study was also subsequently published in the New England Journal of Medicine.
Patients undergoing mechanical ventilation in the ICU often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative oxygen therapy reduces oxygen exposure, diminishes lung and systemic oxidative injury, and thereby decreasing the number of days patients needed mechanical ventilation.
Paul Young, Medical Research Institute of New Zealand, and colleagues randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy.
In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2.
The primary outcome was the number of ventilator-free days from randomization until day 28.
Key findings include:
- The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days and 22.1 days, respectively, for an absolute difference of −0.3 days.
- The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours and 1 hour, respectively (absolute difference, 28 hours); the conservative-oxygen group spent less time with a Spo2 exceeding 96%, with a duration of 27 hours and 49 hours, respectively (absolute difference, 22 hours).
- At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05.
The results, also published simultaneously in the New England Journal of Medicine, are at odds with those of a single-centre study from Italy, published in JAMA in 2016, which was stopped early after interim analysis suggested an increase in deaths associated with higher-dose oxygen therapy.
The concern has been that high levels of blood oxygen resulting from supplementation may harm patients via systemic and pulmonary oxidative injury, Young and colleagues explained. That has prompted efforts to identify supplemental oxygen regimens that don't oversaturate while still preventing hypoxemia.
Young said the new trial data provide "a degree of reassurance" that the findings from the Italian trial represented a false-positive result.
He told MedPage Today that, based on the latest findings, "a prudent approach [to oxygen delivery] for patients on mechanical ventilation in the ICU is the middle ground where one should neither systematically target high levels of oxygen nor aggressively reduce oxygen in a way that exposes patients to hypoxemia."
Subgroup analysis did show that conservative oxygen therapy had a benefit for patients who had suffered sudden cardiac arrest or had other anoxic brain injuries.
"Our findings decrease the probability that the use of our protocol for conservative oxygen therapy in this population would result in markedly lower mortality than the use of usual oxygen therapy. However, the confidence intervals around our mortality estimates are sufficiently wide that we cannot rule out important effects of our conservative oxygen regimen on mortality," the team wrote.
Young said future trials should be powered to detect a true minimally important difference in mortality.
He said the researchers are now working to secure funding for a much larger international trial "designed to test the hypothesis that, compared with usual oxygen therapy, conservative use of oxygen reduces mortality by 1.5 percentage points or greater in adults who are ventilated following an unplanned ICU admission or emergency intubation in the ICU."
More Information: Young P, et al "Conservative oxygen therapy during mechanical ventilation in the ICU" NEJM 2019
Journal Information: New England Journal of Medicine