Association between arterial oxygen tension with clinical outcomes in patients undergoing VA-ECMO support: a systematic review and dose-response meta-analysis
Authors: Ananta M E , Pragitara C F , Wijaya A D , Semedi B P , Widyantoro B 
Published: October 2024

Abstract

Background
Arterial hyperoxia has been associated with a worse prognosis in critically ill patients. However, studies conducted in patients undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) used inconsistent and arbitrary thresholds for defining hyperoxia, which impeded the determination of the optimal target for arterial oxygen tension (PaO2) in this population.

Purpose
To investigate and visualise the dose-response relationship between post-ECMO level of PaO2 with early mortality (in-hospital and 1-month) and poor neurological outcomes in adult patients undergoing VA-ECMO support, including Extracorporeal Cardiopulmonary Resuscitation (ECPR).

Methods
A systematic search was conducted through Pubmed and Embase to include studies that stratified patients based on PaO2 levels and evaluated relevant outcomes. We utilised either adjusted Odds Ratio (OR) with 95% Confidence Interval (CI) when available, or unadjusted OR against the lowest exposure category. The median, mean, or midpoint value of PaO2 was assigned as the corresponding dose. A random-effects one-stage dose-response meta-analysis was performed to assess linear association for every 10 mmHg increase in PaO2, while potential non-linear relationship was explored with restricted cubic splines at 3 knots (10th, 50th, and 90th percentile). Non-linearity was assessed by using Wald test with p value &lt;0.05 considered significant. Statistical analyses were performed using STATA 17.0.

Results
Fourteen eligible records were identified (cardiogenic shock/CS = 5 records; ECPR = 8 records; both = 1 record). Only four studies classified a separate category for hypoxemic patients (&lt;60 mmHg). PaO2 levels were measured within 24-72 hours of VA-ECMO initiation, except in one study. PaO2 level was not associated with early mortality (9 studies; OR 1.021 [95% CI 0.988–1.055]; p for non-linearity = 0.893), but found to have a linear association with composite poor neurological outcomes (6 studies; OR 1.016 [1.009–1.024]; p for non-linearity = 0.346). Subgroup analysis of CS patients revealed a linear association between PaO2 &gt;100 mmHg and early mortality (4 studies; OR 1.025 [95%CI 1.018–1.032]; p for non-linearity = 0.255). For ECPR patients, a J-shaped relationship was observed between PaO2 and early mortality (5 studies; p for non-linearity = 0.004), with the lowest odds being at PaO2 level of 110-210 mmHg, while PaO2 level &gt;110 mmHg showed a linear trend towards higher odds of poor neurological function (4 studies; OR 1.091 [95%CI 0.938–1.269]; p for non-linearity = 0.257).

Conclusion
Pooled data from observational studies suggest that PaO2 &gt;100 mmHg should be avoided in CS patients on VA-ECMO support, given its linear association with mortality, but it cannot be extrapolated to hypoxemic patients. In ECPR patients, PaO2 level around 110-210 mmHg conferred the best clinical outcomes. However, these findings should be confirmed through randomised controlled trials.