Abstract

Background Many patients in the ICU receive oxygen to secure blood and tissue oxygenation. Increasing evidence shows exposure to high fractions of inhaled oxygen (FiO2) being associated with adverse effects. In patients with severe ARDS, veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) can be implemented as a rescue therapy and PaO2 levels can be controlled by the blood flow of the VV-ECMO. Yet, optimal oxygenation targets in ARDS patients treated with VV-ECMO are unknown.

Methods Retrospective analysis of 443 patients with severe ARDS treated with VV-ECMO. Regression analyses were performed for mortality and time-weighted averages of PaO2 and FiO2. Furthermore, considering a possible non-linear relationship, a restricted cubic spline (RCS) model was performed for PaO2.

Results A simple logistic regression for mean PaO2 and ICU mortality showed a significant positive association (per mmHg OR 0.99 [95%CI 0.98-1.00], p=0.002). RCS analysis showed a U-shaped association of mortality and mean paO2 (paO2 69.70-90.24mmHg: OR 0.92 [95%CI 0.89-0.94], p<0.001; paO2 90.24-123.40mmHg: OR 1.09 [95%CI 1.06-1.13], p<0.001). A model including PaO2 as RCS variable and FiO2 showed significant associations of mortality with both variables (PaO2 69.70-90.24mmHg: OR 0.94 [95%CI 0.91-0.97], p<0.001; paO2 90.24-123.40 mmHg: OR 1.07 [95%CI 1.04-1.11], p<0.001; FiO2: OR 35.98 [95%CI 8.67-158.60], p<0.001, VIF<1.11).

Conclusions PaO2-levels in patients with ARDS and VV-ECMO have a U-shaped association with mortality. Optimal outcomes are observed in the 90-123 mmHg range, which is higher compared to non-ECMO settings. Whether this is explainable by increased tissue oxygenation with concurrent avoidance of pulmonary hypoxia should be subject of future research.

Research Letter Optimal oxygen target levels for critically ill patients requiring mechanical ventilation have been discussed for decades and recent guidelines recommend PaO2-levels between 70 and 90 mmHg.1–3 In contrast, very low but also high PaO2-levels were both associated with higher mortality, yielding a U-shaped association between PaO2 and mortality.4–6 In patients with ARDS and refractory hypoxemic respiratory failure, veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) can be implemented as a rescue therapy and PaO2-levels can be controlled by the blood flow of the VV-ECMO.7 Yet, optimal oxygenation targets in ARDS patients treated with VV-ECMO are unknown.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research was supported by institutional sources. Dr Buenger is supported by the Rahel Hirsch Programme of Charite-Universitaetsmedizin Berlin. Dr Buenger and Luigi La Via are participants in the ESAIC Mentorship Programme (ESAIC_MSP_2024_VB).

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the Medical Ethics Committee of the Charite-Universitaetsmedizin Berlin EA2/019/19.

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Data Availability

Data are available from the corresponding author on reasonable request.

AbbreviationsICUintensive care unitARDSacute respiratory distress syndromeECMOextracorporeal membrane oxygenationpaO2partial pressure of oxygenFiO2fraction of inhaled oxygenPEEPpositive end-expiratory pressureRCSrestricted cubic spline