Exposure to severe hyperoxemia worsens survival and neurological outcome in patients supported by veno-arterial extracorporeal membrane oxygenation: A meta-analysis

Background: Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a rescue treatment in refractory cardiogenic shock (CS) or refractory cardiac arrest (CA). Exposure to hyperoxemia is common during VA-ECMO, and its impact on patient's outcome remains unclear. Methods: We conducted a systematic review (PubMed and Scopus) and meta-analysis investigating the effects of exposure to severe hyperoxemia on mortality and poor neurological outcome in patients supported by VA-ECMO. When both adjusted and unadjusted Odds Ratio (OR) were provided, we used the adjusted one. Results are reported as OR and 95% confidence interval (CI). Subgroup analyses were conducted according to VA-ECMO indication and hyperoxemia thresholds. Results: Data from 10 observational studies were included. Nine studies reported data on mortality (n = 5 refractory CA, n = 4 CS), and 4 on neurological outcome. As compared to normal oxygenation levels, exposure to severe hyperoxemia was associated with higher mortality (nine studies; OR: 1.80 [1.16-2.78]; p = 0.009; I2 = 83%; low certainty of evidence) and worse neurological outcome (four studies; OR: 1.97 [1.30-2.96]; p = 0.001; I2 = 0%; low certainty of evidence). Magnitude and effect of these findings remained valid in subgroup analyses conducted according to different hyperoxemia thresholds (>200 or >300 mmHg) and VA-ECMO indication, although the association with mortality remained uncertain in the refractory CA population (p = 0.13). Analysis restricted to studies providing adjusted OR data confirmed an increased likelihood of poorer neurological outcome (three studies; OR: 2.11 [1.32-3.38]; p = 0.002) in patients exposed to severe hyperoxemia but did not suggest higher mortality (five studies; OR: 1.68 [0.89-3.18]; p = 0.11). Conclusions: Severe hyperoxemia exposure after initiation of VA-ECMO may be associated with an almost doubled increased probability of poor neurological outcome and mortality. Clinical efforts should be made to avoid severe hyperoxemia during VA-ECMO support.