By Samuel Nadler, MD, PhD
Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle
SYNOPSIS: In this one-year follow-up to the HOT-ICU trial examining higher vs. lower oxygenation targets for patients with hypoxemic respiratory failure, there were no differences in mortality or quality of life measurements between groups.
SOURCE: Crescioli E, Klitgaard TL, Poulsen LM, et al. Long-term mortality and health-related quality of life of lower versus higher oxygenation targets in ICU patients with severe hypoxaemia. Intensive Care Med 2022;48:714-722.
Hypoxemic respiratory failure is a common cause of intensive care unit (ICU) admission. Treatment entails giving patients supplemental oxygen to correct hypoxemia. The HOT-ICU trial randomized 2,928 patients across seven countries who required at least 10 L/minute supplemental oxygen to a PaO2 target of either 60 mmHg or 90 mmHg.1 This trial achieved differences in median PaO2 between the groups (70.8 mmHg vs. 93.3 mmHg). The current study is an extension of this trial reporting on pre-specified one-year outcomes, including all-cause mortality and two measures of quality of life.
The initial HOT-ICU trial demonstrated no significant differences in 90-day mortality with lower vs. higher O2 targets.1 The lower and higher O2 groups were predominantly older (median age 70 years in each group), male (63.7% and 64.9%, respectively), and admitted to medical ICUs (85.9% and 85.1%, respectively) with a primary diagnosis of pneumonia (57.7% and 57.4%, respectively). Ethnic backgrounds of patients were not reported. Most patients in the lower and higher O2 groups required invasive mechanical ventilation (57.4% and 59.7%, respectively) with median PaO2/FiO2 ratios of 118.6 and 117.5, respectively. The 90-day mortality was 42.9% and 42.4% (P = 0.64). In the follow-up study, one-year mortality was 49% and 48.7%, respectively (P = 0.92). Neither metric for quality of life, EuroQol visual analogue scale (EQ-VAS) nor EuroQol five dimensions five level (EQ-5D-5L) questionnaire, identified differences between the two groups at one year.
COMMENTARY
Since the publication of the single-center Oxygen-ICU trial in 2016 that reported decreased ICU mortality with lower oxygenation targets, the optimal level of oxygen supplementation for patients with hypoxemic respiratory failure has remained in question.2 The HOT-ICU trial published in 2021 did not replicate these results in a larger, multicenter study. The primary outcome of 90-day mortality as well as secondary outcomes of days alive without life support or alive after hospital discharge were not statistically different, although no assessment of quality of life was included in the study. Notably, the 90-day mortality in the conservative and liberal groups of HOT-ICU (42.9% and 42.4%, respectively) was considerably higher than the ICU mortality in each group in the Oxygen-ICU study (11.6% and 20.2% for lower and higher O2 groups, respectively). This is thought to be because of the higher percentage of surgical patients in the Oxygen-ICU study. The one-year follow-up data in the study by Crescioli et al echo the high mortality within the mostly medical ICU patient group. The lower oxygenation group had a one-year mortality of 49%, and the higher oxygenation group one-year mortality was 48.7%. In each group, there was an additional mortality of approximately 6% in the nine-month follow-up period. Furthermore, more than 40% of patients alive at one year reported moderate, severe, or extreme problems with mobility and performance of usual activities, nearly 40% reported moderate or worse pain, and about 20% reported moderate or worse anxiety/depression. Overall, the morbidity and mortality of patients with hypoxemic respiratory failure was high in the HOT-ICU trial.
Several important lessons can be learned from this trial. First, lower oxygenation targets in patients with hypoxemic respiratory failure do not lead to better long-term outcomes. While other studies have looked at short-term outcomes, this study represents the largest long-term study on this topic. Second, a higher oxygenation target did not lead to worse long-term mortality or quality of life. Therefore, a lower PaO2 target appears safe. Efforts at treating the underlying cause of hypoxemia are important, but pushing PaO2 from 60 mmHg to 90 mmHg does not in itself seem to affect long-term outcomes.
REFERENCES
- Schjorring OL, Klitgaard TL, Perner A, et al. Lower or higher oxygen targets for acute hypoxemic respiratory failure. N Engl J Med 2021;384:1301-1311.
- Giradis M, Busani S, Damiani E, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: The Oxygen-ICU randomized clinical trial. JAMA 2016;316:1583-1589.
