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Conservative oxygen therapy in the ICU reduces mortality

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‘Little downside’ seen to careful oxygen titration

The reduction in mortality seen with conservative oxygen therapy in the Oxygen-ICU trial was “striking,” according to editorialist Dr. Niall D. Ferguson. However, “it is likely that to some extent, this trial has overestimated the true treatment effect of conservative oxygen therapy,” he cautions, given baseline imbalances between groups, early stopping based in part on an unplanned interim analysis, and the small number of deaths. The editorialist noted that the study was underpowered and criticized its use of a modified intent-to-treat analysis.

The trial’s findings contrast with those of a pilot study conducted by the ANZICS clinical trials group that did not find better outcomes with use of lower oxygen targets, according to Dr. Ferguson. However, in that trial, both arms had lower target and actual PaO2 levels. Thus, the optimal clinical approach remains uncertain.

Dr. Niall D. Ferguson

Dr. Niall D. Ferguson

“It is important to recognize that this study [Oxygen-ICU] is not a trial of permissive hypoxemia, which has been proposed but is as yet a completely unproven therapeutic strategy. This trial involved targeting relative normoxia, avoiding both significant desaturations and exposure to supraphysiological PaO2,” he points out.

“Until the results of further trials addressing this issue are available, there appears to be little downside in the careful titration and monitoring of supplemental oxygen in the ICU to achieve physiologically normal levels of PaO2 while avoiding potentially dangerous hyperoxia,” he concludes.

Dr. Ferguson disclosed that he has no relevant conflicts of interest.

Niall D. Ferguson, MD, MSc, is with the Interdepartmental Division of Critical Care Medicine and Departments of Medicine and Physiology, University of Toronto; the Institute of Health Policy, Management, & Evaluation, University of Toronto; the Division of Respirology, Department of Medicine, University Health Network and Mount Sinai Hospital; and the Toronto General Research Institute.


 

FROM ESICM CONGRESS 2016

A strategy of conservatively controlling oxygen delivery to patients in the intensive care unit results in lower mortality than the conventional, more liberal approach whereby patients are often kept in a hyperoxemic state, finds a randomized controlled trial.

The trial, known as Oxygen-ICU, enrolled more than 400 adult ICU patients from an Italian center. Initially planned to last 2 years, it was terminated early because of slow enrollment after an earthquake reduced ICU capacity, with the decision supported by positive results of an interim analysis.

Patients had an absolute nearly 9% lower risk of dying in the ICU with use of the conservative oxygen strategy as compared with the conventional one, according to data reported at the annual congress of the European Society of Intensive Care Medicine and simultaneously published (JAMA. 2016 Oct 5. doi: 10.1001/jama.2016.11993).

“To our knowledge, this is the first randomized clinical trial to evaluate the effect of a conservative oxygen therapy on mortality compared with a standard, more liberal approach in a medical-surgical population of adult critically ill patients,” write the investigators, who were led by Massimo Girardis, MD, of the Intensive Care Unit, Department of Anesthesiology and Intensive Care, University Hospital of Modena (Italy).

Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy compared with conventional therapy resulted in a lower ICU mortality,” they conclude. “However, these preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of such conservative oxygen therapy in critically ill patients.”

In the trial, consecutive patients were randomized evenly to receive conservative oxygen therapy (maintenance of PaO2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation [SpO2] between 94% and 98%) or conventional oxygen therapy (allowance of PaO2 values up to 150 mm Hg or SpO2 values between 97% and 100%) on an open-label basis.

The originally targeted enrollment was 660 patients, but the study was stopped early after only 480 patients had been enrolled.

Results of modified intent-to-treat analyses showed that daily time-weighted PaO2 averages during patients’ ICU stays were higher in the conventional group than in the conservative group (median PaO2, 102 vs. 87 mm Hg; P less than .001).

The rate of ICU mortality, the trial’s primary endpoint, was 11.6% with conservative therapy, about half of the 20.2% seen with conventional therapy (absolute mean difference, 0.086; P = .01).

The conservative group also had lower rates of shock (3.7% vs. 10.6%, P = .006), liver failure (1.9% vs. 6.4%, P = .02), and bacteremia (5.1% vs. 10.1%, P = .049). And they spent a day less on the ventilator (median mechanical ventilation–free hours, 72 vs. 48; P = .02).

Lengths of ICU stay and hospital stay did not differ between the two groups.

One of the study authors reports serving as the data monitoring chair for a phase II study sponsored by InflaRx, on the antibiotic advisory board for Bayer, and on sepsis advisory boards for Biotest and Merck. The study was supported by the National Fund for Scientific Research of the University of Modena and Reggio Emilia.

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