Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study

Fabiana Madotto, Emanuele Rezoagli, Tài Pham, Marcello Schmidt, Bairbre McNicholas, Alessandro Protti, Rakshit Panwar, Giacomo Bellani, Eddy Fan, Frank van Haren, Laurent Brochard, John G Laffey, LUNG SAFE Investigators and the ESICM Trials Group

Abstract

Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study.

Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia).

Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47).

Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort.

Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073.

Keywords: Acute respiratory distress syndrome; Hyperoxemia; Hyperoxia; Hypoxemia; Hypoxia; Invasive mechanical ventilation; Mortality; Oxygen therapy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart describing criteria used to select and to classify the ARDS study population
Fig. 2
Fig. 2
Arterial oxygen tensions and use of oxygen in patients on days 1 and 2 of ARDS. a The distribution of PaO2 on day 1 of ARDS, demonstrating a wide range of PaO2. b Density distributions of PaO2 on days 1 (red line) and day 2 (blue line) of ARDS. c Histogram of FIO2 and PaO2 on day 1 of ARDS. d Histogram of FIO2 and PaO2 on day 2 of ARDS. Note: in c and d, each bar is segmented into hyperoxemia (black), normoxemia (dark gray), hypoxemia (light gray), and unknown (white) component
Fig. 3
Fig. 3
Use of inspired oxygen in patients on days 1 and 2 of ARDS. a A box plot of PaO2 at each decile of FIO2 uses on day 1 of ARDS. b A box plot of FIO2 used on day 1 and 2 of ARDS in the study population classified by PaO2 on day 2 (hypoxemia, normoxemia, hyperoxemia, and unknown). c A box plot of PaO2 at each decile of FIO2 used on day 2 of ARDS
Fig. 4
Fig. 4
Relationship between oxygen and outcome in patients with ARDS. a A locally estimated scatterplot smoothing (LOESS) of the relationship between PaO2 on day 1 of ARDS and mortality risk. b A LOESS of the relationship between PaO2 use on day 2 of ARDS and mortality risk. c A LOESS of the relationship between FIO2 use on day 1 in non-hypoxemic patients with ARDS and mortality risk. d A LOESS of the relationship between FIO2 use on day 2 in non-hypoxemic patients with ARDS and mortality risk. Note: LOESS uses a bandwidth 2/3 and 1 degree of polynomial regression
Fig. 5
Fig. 5
Kaplan-Meier curves for hospital survival in matched samples. a Survival probability in matched sample (n = 448) of patients with sustained normoxemia and with sustained hyperoxemia. b Survival probability in matched sample (n = 646) of patients with normoxemia and with excess oxygen use at day 1. Notes: (1) Normoxemia is defined as 55 mmHg ≤ PaO2 ≤ 100 mmHg on day 1 of ARDS, sustained normoxemia defined as normoxemia on day 1 and 2 of ARDS, sustained hyperoxemia defined as PaO2 > 100 mmHg on day 1 and 2 of ARDS, and excess oxygen use defined as PaO2 > 100 mmHg and FIO2 ≥ 0.60 on day 1 of ARDS. (2) Mortality is defined as mortality at hospital discharge or at 90 days, whichever event occurred first. We assumed that patients discharged alive from the hospital before 90 days were alive on day 90. (3) The number of patients at risk reported at the bottom of the figure is referred to as the end of the corresponding day

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