Conservative or liberal oxygen targets in patients on venoarterial extracorporeal membrane oxygenation

Abstract

Purpose: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia.

Methods: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO₂ 92-96%) or to a liberal oxygen strategy (target SaO₂ 97-100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months.

Results: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0-13.7] versus liberal: 0 days [IQR 0-13.7], median treatment effect: 0 days [95% confidence interval (CI) - 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001).

Conclusions: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28.

Keywords: ECMO; Extracorporeal membrane oxygenation; Hyperoxaemia; Hyperoxia; Oxygen target.

Fig. 1

Partial pressures of arterial oxygen and oxygen saturations of the patient and post-oxygenator. Shown are the partial pressures (panels a., b.) and saturations (panels c.–e.) of oxygen recorded from the post-oxygenator (PbO₂, SbO₂), the radial arterial line (PaO₂, SaO₂) and pulse oximetry on the right hand (SpO₂) of patients still on ECMO from day 1 to 7. Patients were assigned to either a conservative oxygen strategy (SaO₂ 92–96%) or to a liberal oxygen strategy (SaO₂ 97–100%) at the time of randomization. The intervention strategy was continued until cessation of ECMO. One patient in the conservative group who died on day 1, had no blood gas values recorded. All curves show the geometric mean and 95% confidence interval of the available values

Fig. 2

Overall and subgroup analyses of difference in medians for intensive care unit (ICU)-free days to day 28. Shown are the results of analysis of difference in medians for ICU-free days to day 28 between the conservative oxygen strategy (SaO₂ 92–96%) group and the liberal oxygen strategy (SaO₂ 97–100%) group. Groups shown include the whole 300 patient cohort included in the ‘intention-to-treat’ analysis, 254 patients included in the per-protocol analysis, pre-specified subgroups of 184 patients aged above 50 years, 116 patients aged 50 years or less, 160 patients with a SAVE score of – 5 or less, 130 patients with a SAVE score of more than – 5, 176 patients randomised within three hours or less from VA-ECMO cannulation, 124 patients randomised more than three hours from VA-ECMO cannulation, 192 patients who underwent VA-ECMO for cardiogenic shock and 108 patients who received ECMO cardio-pulmonary resuscitation. VA-ECMO venoarterial extracorporeal membrane oxygenation, SAVE Survival After Venoarterial ECMO score

Fig. 3

Patient survival. Conservative vs liberal; Raw hazard ratio 0.97 [0.70 to 1.36]. Adjusted hazard ratio* 0.92 [0.65–1.31]. *Adjusted for site, ECMO indication, age, diagnosis & time from ECMO initiation to randomisation