BackgroundThe implantation of venovenous extracorporeal membrane oxygenation (VV-ECMO) support to manage severe acute respiratory distress syndrome generates large variations in carbon dioxide partial pressure (PaCO2) that are associated with intracranial bleeding. We assessed the feasibility and efficacy of a pragmatic protocol for progressive dual titration of sweep gas flow and minute ventilation after VV-ECMO implantation in order to limit significant PaCO2variations.Patients and methodsA protocol for dual titration of sweep gas flow and minute ventilation following VV-ECMO implantation was implemented in our unit in September 2020. In this single-centre retrospective before-after study, we included patients who required VV-ECMO from March, 2020 to May, 2021, which corresponds to two time periods: from March to August, 2020 (control group) and from September, 2020 to May, 2021 (protocol group). The primary endpoint was the mean absolute change in PaCO2in consecutive arterial blood gases samples drawn over the first 12 h following VV-ECMO implantation. Secondary endpoints included large (> 25 mmHg) initial variations in PaCO2, intracranial bleedings and mortality in both groups.ResultsFifty-one patients required VV-ECMO in our unit during the study period, including 24 in the control group and 27 in the protocol group. The protocol was proved feasible. The 12-h mean absolute change in PaCO2was significantly lower in patients of the protocol group as compared with their counterparts (7 mmHg [6–12] vs. 12 mmHg [6–24],p= 0.007). Patients of the protocol group experienced less large initial variations in PaCO2immediately after ECMO implantation (7% vs. 29%,p= 0.04) and less intracranial bleeding (4% vs. 25%,p= 0.04). Mortality was similar in both groups (35% vs. 46%,p= 0.42).ConclusionImplementation of our protocol for dual titration of minute ventilation and sweep gas flow was feasible and associated with less initial PaCO2variation than usual care. It was also associated with less intracranial bleeding.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13613-023-01138-5.