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Conservative Oxygen Approach Again Fails in ICU

— But not risky either in HOT ICU trial, unlike some recent results

MedpageToday
A close up of a mechanical ventilation machine in the ICU

Lower oxygenation targets for critically ill respiratory failure patients weren't any better for survival, the showed.

Targeting a partial pressure of arterial oxygen (PaO2) of 60 mm Hg didn't impact 90-day mortality compared with a target of 90 mm Hg (42.9% vs 42.4%, adjusted RR 1.02, 95% CI 0.94-1.11), reported Bodil Rasmussen, MD, PhD, of Aalborg University Hospital in Denmark, and colleagues.

The same was true for other 90-day endpoints, including percentage of days alive without life support, the percentage of days alive after hospital discharge, and serious adverse events, the group noted in the in conjunction with the virtual .

"Our findings lend weight to the utility of conservative oxygen therapy in patients with acute hypoxemic respiratory failure, as compared with the results of the LOCO2 trial," the group concluded.

That 200-patient trial included only acute respiratory distress syndrome (ARDS) patients, whereas HOT ICU had broader inclusion criteria (12.8% had ARDS). Still, baseline PaO2 to fraction of inspired oxygen (FiO2) ratios were "remarkably similar" between trials, Rasmussen's group noted.

LOCO2 raised concerns because 28-day mortality was a nonsignificant 7.8 percentage points higher (34.3% vs 26.5%) with conservative targets of 55-70 mm Hg and oxygen saturation (SpO2) of 88% to 92% versus targeting 90-105 mm Hg PaO2 and ≥96% SpO2. The conservative approach had significantly higher 90-day mortality (44.4% vs 30.4%) and more cases of mesenteric ischemic events.

Intestinal ischemia in HOT ICU was similar in incidence between the two groups.

The ICU-ROX trial of conservative oxygen in a broader mechanically ventilated population likewise showed a slight numeric excess of 180-day mortality with a conservative oxygen saturation target of 90% to 96% and no earlier weaning versus usual care.

At the time those trials were published, an argued that neither trial was large enough to rule out a null effect but that "avoiding excess oxygen (i.e., not administering supplemental oxygen when the SpO2 is 96% or greater and not starting supplemental oxygen when the SpO2 is 92% or 93%) seems sensible, as per recent guidelines."

HOT ICU, while much larger, likewise could not "preclude the possibility of clinically important harm or benefit with a lower oxygenation strategy in this population or in other types of critically ill patients," Rasmussen's group noted.

The trial included 2,928 adults randomized to oxygen targets within 12 hours of admission to the ICU and who were on at least 10 L/min of oxygen in an open system or had a FiO2 of at least 0.50 in a closed system.

It did not explicitly include or exclude COVID-19 patients during the study period that ran from June 2017 through August 2020 at 35 ICUs across seven European countries. However, oxygenation strategies in COVID-19 respiratory failure have largely mirrored those in the ICU due to other causes.

The conservative and liberal oxygen groups were similar in use of mechanical ventilation, prone positioning, inhaled vasodilators, extracorporeal membrane oxygenation, circulatory support, dialysis, and blood transfusions, as well as positive end-expiratory pressure, peak inspiratory pressure, and tidal volume of invasive mechanical ventilation or in end-expiratory pressure with noninvasive ventilation.

Disclosures

The trial was supported by a grant from Innovation Fund Denmark, by the Aalborg University Hospital, by grants from the Regions of Denmark, by a grant from the Obel Family Foundation, by the Danish Society of Anesthesiology and Intensive Care Medicine, and by the Intensive Care Symposium Hindsgavl.

Rasmussen reported grants from the Innovation Foundation Denmark, the Obel Family Foundation, the Regions of Denmark, the Novo Nordisk Foundation, and the Danish Ministry of Higher Education and Science.

Primary Source

New England Journal of Medicine

Schjørring OL, et al "Lower or higher oxygenation targets for acute hypoxemic respiratory failure" N Engl J Med 2021; DOI: 10.1056/NEJMoa2032510.