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February - 2021


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Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure

O Schjorring, T Klitgaard, A Perner, et al for the HOT-ICU Investigators NEJM, 2021, online Jan 2021


The ideal oxygenation target range for patients with acute hypoxemic respiratory failure remains unresolved. There is evidence supporting lower target oxygen range as preferable or equivalent;

  • A small multicentre study reported no harm from a peripheral SpO2 range of 88-92%  vs >96%
  • A single centre RCT reported lower mortality for patients in the PaO2 range 70-100 mmHg vs up to 150 mmHg
  • Meta-analysis reported lower oxygenation targets preferable
  • ICU-ROX reported no difference in VFDs or 28-d mortality. 

In contrast, the ARDS LOCO trial was stopped early because of a higher incidence of mesenteric ischaemia and 90-d mortality in the lower oxygenation group.

The Handling Oxygenation Targets in the ICU (HOT-ICU) trial contributes to this field. What did they do?

  • Randomised 2928 adults with acute hypoxemic respiratory failure in ICU (10 l/m or 0.5 FiO2) to;
  • Lower oxygenation group (PaO2 60 mmHg) vs Higher oxygenation group (PaO2 90 mmHg) until a maximum of 90-days
  • 60% had pneumonia, 13% ARDS, 58% ventilated, median PaO2 77 mmHg, FiO2 0.70, P:F 118
  • Primary outcomes was 90d mortality 42.9% lower vs 42.4% higher group, adj RR 1.02 95% CI 0.94-1.11, p=0.64
  • No difference in secondary outcomes ( days alive, incidence of shock, AMI, stroke, intestinal ischaemia) 

In 2928 adults in ICU with acute hypoxaemic respiratory failure (mean P:F 118), an oxygen target of PaO2 60 mmHg vs 90 mmHg did not result in lower 90-d mortality, or secondary outcomes including mesenteric ischaemia and HIE. The authors note the higher than expected 90d mortality (42%), and note the higher incidence of medical patients (85%) compared to previous studies.




Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target.


In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days.


At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P=0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P=0.24).


Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days


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