Time-Dependent Effects of Inotropic Exposure During Venoarterial Extracorporeal Membrane Oxygenation Support on the Probability of Extracorporeal Membrane Oxygenation Weaning Failure

Objectives: During venoarterial extracorporeal membrane oxygenation (VA ECMO), organ perfusion no longer entirely depends on native cardiac output, which may reduce the therapeutic advantage of inotropic drugs relative to their risks. We hypothesized that, in this setting, higher cumulative inotropic exposure would be associated with impaired cardiac recovery. Design: Observational cohort study on the effects of longitudinal inotropic exposure during VA ECMO support. Temporal changes in inotropic support during VA ECMO support were evaluated. Cumulative inotropic exposure per day during VA ECMO support was calculated using the area under the curve of a standardized inotropic score. These cumulative inotropic scores were associated with the risk of ECMO weaning failure up to 30 days (a composite of death, ongoing need for ECMO support, or the need for heart replacement therapy), mortality, and complications, using joint modeling techniques. Setting: Six hospitals in the Netherlands. Patients: Adult patients with severe cardiogenic shock (CS) receiving VA ECMO support between 2018 and 2024. Interventions: None. Measurements and Main Results: Out of 440 patients with various causes of CS, 235 patients (53.4%) developed ECMO weaning failure. Inotropic support remained largely unchanged in the days following VA ECMO initiation. Adjusted joint models showed that a higher cumulative inotropic exposure during VA ECMO support was associated with an increased risk for ECMO weaning failure (hazard ratio [HR], 1.04; 95% CI, 1.00–1.07), 30-day mortality (HR, 1.04; 95% CI, 1.01–1.08), arrhythmias (HR, 1.05; 95% CI, 1.01–1.08), and protracted lactate clearance (HR, 0.96; 95% CI, 0.92–0.99). Conclusions: In patients requiring VA ECMO support for refractory CS, inotropic support is often maintained at similar levels after ECMO initiation. Higher cumulative inotropic exposure was associated with an increased risk for ECMO weaning failure. Prospective studies are needed to investigate whether inotropes can be tapered or even stopped and whether such a strategy could improve cardiac recovery.