Mathematical model simulations may assist in the selection of mechanical ventilator settings. Previously, simulations have been limited to control ventilator modes, as these models lacked representation of respiratory control. This paper presents integration of a chemoreflex respiratory control model with models describing: ventilation and pulmonary gas exchange; oxygenation and acid-base status of blood; circulation; interstitial fluid and tissue buffering; and metabolism. A sensitivity analysis showed that typical response to changing ventilator settings can be described by base excess (BE), production of CO2 (VCO2), and model parameters describing central chemoreceptor behavior. Since BE and VCO2, can be routinely measured, changes in ventilator support may therefore be used to identify patient-specific chemoreceptor drive, enabling patient-specific predictions of the response to changes in mechanical ventilation.