Patients suffering acute lung failure depend on artificial ventilation in order to survive. In severe cases, this therapy may not be sufficient any more and long term extracorporeal membrane oxygenation (ECMO) may be used as a last chance rescue therapy. Adapted from short term cardiopulmonary bypass, these machines now need an increased ability for autonomous and unsupervised operation. Apart from the material aspects (hemolysis and long term biocompatibility), a prerequisite for safe and reliable operation is the implementation of an adequate automation and safety scheme. Extending previous work [1,2] where we focused on machine internal control and the modeling of the biological process, this paper presents an integrated control of the physiological target values.