Background: The efficiency of venovenous extracorporeal membrane oxygenation (VV ECMO) may be influenced by cannula configuration, potentially affecting oxygenation and the ability to apply ultra-protective ventilation in severe ARDS.

Materials and methods: This retrospective single-center study included all adult patients with severe ARDS supported with femoro-jugular VV ECMO between January 2013 and December 2022. Patients were divided into two groups according to cannula configuration: cross configuration (CC) and non-cross configuration (NCC). Ventilatory parameters, mechanical power, blood gases, and ECMO settings were analyzed at 1, 4, 12, and 24 h after ECMO initiation. A longitudinal analysis using generalized estimating equations adjusted for APACHE II score, COVID-19 ARDS, and baseline mechanical power was performed.

Results: Sixty-two patients were included (CC, n = 33; NCC, n = 29). Patients had a median age of 56 [50-63] years, 66% were male, and 58% had COVID-19 ARDS. Baseline respiratory parameters, ECMO settings, and cardiac output were comparable between groups. Compared with NCC, the CC group had significantly lower FiO₂ (21 [21-27] vs. 60 [40-100]%, p < 0.0001), and mechanical power (6.5 ± 2.4 vs. 12.3 ± 6.2 J/min, p < 0.0001) at 1 h, with sustained differences up to 24 h. In adjusted longitudinal analysis, the adjusted difference in mechanical power between CC and NCC was6.80 J/min (95% CI 3.82-9.78, p < 0.001) at 1 h and 6.69 J/min (95% CI 3.62-9.77, p < 0.001) at 24 h, with no significant interaction over time (p = 0.681). Sensitivity analyses including additional adjustment for prone positioning, baseline compliance, and time from intubation to ECMO initiation showed consistent results.

Conclusion: Cross cannula configuration is associated with reduced mechanical ventilation intensity during VV ECMO, independent of disease severity and ARDS etiology. These findings suggest improved ECMO efficiency and support further evaluation in prospective studies.