  Combined extracorporeal membrane oxygenation (ECMO) and continuous renal
replacement therapy (CRRT) pose complex hemodynamic challenges in intensive
care. In this study, a comprehensive lumped parameter model (LPM) is developed
to simulate the cardiovascular system, incorporating ECMO and CRRT circuit
dynamics. The model is used to analyze nine CRRT-ECMO connection schemes under
varying flow conditions. Using a robust parameter identification framework
based on global sensitivity analysis (GSA) and multi-start gradient-based
optimization, we calibrated the model on 30 clinical data points from eight
veno-arterial ECMO patients.
  Our results indicate that CRRT has a significant impact on the cardiovascular
system, with changes in pulmonary artery pressure of up to 202.5 %, highly
dependent on ECMO flow. The GSA proved to be a powerful tool to improve the
parameter estimation process. The established parameter estimation framework is
fast and robust without the need for hyperparameter tuning and improves the
parameter estimation process with an R^2>0.98 between simulation and
experimental data. It uses modeling methods that could pave the way for
real-time applications in intensive care.
  This open-source framework provides a valuable tool for the systematic
evaluation of combined ECMO and CRRT, which can be used to develop standardized
treatment protocols and improve patient outcomes in critical care. In addition,
as a digital twin, this model also provides a good basis for addressing
research questions related to mechanical circulatory and respiratory support.
