Lower oxygenation target in ICU does not improve mortality

In patients with acute hypoxemic respiratory failure admitted to the intensive care unit (ICU), a lower oxygenation target does not lead to a lower mortality rate, according to results of the HOT-ICU* trial presented at eCCR 2021.

“Patients with acute hypoxemic respiratory failure in the ICU are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear,” said the authors.

“[W]e found that targeting a PaO₂** of 60 mmHg rather than a PaO₂ of 90 mmHg did not result in better values for several key outcomes – including mortality, the percentage of days alive without life support, the percentage of days alive after hospital discharge, and serious adverse events (AEs) – at 90 days,” they said.

Participants in this multicentre study were 2,928 adults with acute hypoxemic respiratory failure who had been admitted to the ICU within the past 12 hours and were recipients of oxygen at ≥10 L/minute (open system) or had an FiO₂** of ≥0.50 (closed system). They were randomized 1:1 to receive oxygen therapy with a PaO₂ target of either 60 or 90 mmHg (low and high oxygenation group, respectively) for ≤90 days. The primary analysis included 1,441 and 1,447 patients in the low and high oxygenation group, respectively.

Baseline characteristics were generally comparable between the two groups, except for cardiac arrest which was more common in the high vs low oxygenation group (12.8 percent vs 10.3 percent). Median age was 70 years and 63.7 and 64.9 percent of the low and high oxygenation groups, respectively, were male. There was a median 4 days between ICU admission and randomization. Median baseline PaO₂ was 77.3 mmHg in both groups and median FiO₂ was 0.70. The use of mechanical ventilation, prone positioning, inhaled vasodilators, extracorporeal membrane oxygenation, circulatory support, renal-replacement therapy, and blood transfusions was comparable between groups.

At 90 days, mortality rate did not significantly differ between patients with lower and higher oxygen targets (42.9 percent vs 42.4 percent; adjusted risk ratio [RR], 1.02, 95 percent confidence interval, 0.94–1.11; p=0.64). [eCCR 2021; N Engl J Med 2021;doi:10.1056/NEJMoa2032510]

The percentage of days alive without life support (no mechanical ventilation, renal-replacement therapy, or vasopressor or inotrope infusion) at 90 days did not significantly differ between patients in the low and high oxygenation group (median 87.8 percent vs 84.4 percent; p=0.10), nor did the percentage of days alive post-discharge from hospital (median 55.6 percent vs 50.0 percent; p=0.67).

A comparable proportion of patients in the low and high oxygenation groups experienced ≥1 serious adverse events (36.1 percent vs 38.1 percent; RR, 0.95; p=0.24), specifically new episodes of shock (33.9 percent vs 35.8 percent), myocardial ischaemia (1.0 percent vs 0.5 percent), cerebral ischaemia (1.3 percent vs 1.6 percent), or intestinal ischaemia (2.2 percent vs 2.0 percent).

Prior studies have suggested that a lower peripheral oxygen saturation target results in comparable or improved outcomes compared with a higher target without contributing harm. [Am J Respir Crit Care Med 2016;193:43-51; JAMA 2016;316:1583-1589] However, negative outcomes such as higher rates of 90-day mortality and mesenteric ischaemia have also been noted with lower vs higher oxygenation targets. [N Engl J Med 2020;382:999-1008]

“Our findings lend weight to the utility of conservative oxygen therapy in patients with acute hypoxemic respiratory failure,” the authors said. “At the same time, the results … do 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.”

The authors pointed out that patients in this trial had more severe hypoxemic respiratory failure than expected, which in turn may have led to higher mortality rates than in previous studies. As such, the results may not be generalizable to a lower-risk population. There were also differences in the effects of treatment in the different ICUs in the trial.