The present invention relates to non-invasive determination of the effective lung volume [ELV], cardiac output, effective pulmonary blood flow [EPBF] and/or the carbon dioxide content of venous blood of a mechanically ventilated subject (3). The subject (3) is ventilated using a ventilation pattern comprising at least one phase of decreased ventilation and at least one phase of increased ventilation, wherein each of said phases comprises at least two breaths during which a level of CO2 expired by said subject assumes a substantially steady state (SS1, SS2). At least one of said phases of decreased and increased ventilation comprises at least a first breath for generating a substantial change in the level of expired CO2 compared to a preceding breath, and at least a second breath being different in duration and/or volume than said first breath, for causing the level of expired CO2 to assume said substantially steady state (SS1, SS2).