The gradient between end-tidal partial pressure of CO 2 (PETCO 2 ) and arterial partial pressure of CO 2 (PaCO 2 ) (PET-aCO 2 ) in mechanically ventilated patients presents a wide range of variation [95] . The reduction of the PET-aCO 2 gradient can be achieved in spontaneously breathing healthy humans using an end-inspiratory rebreathing technique, which equilibrates end-tidal, alveolar, arterial and venous PCO 2 . Based on the aforementioned, Fierstra et al. [96] investigated whether this method would reduce the PET-aCO 2 gradient in a ventilated animal model. This technique led to a reduction in the PET-aCO 2 gradient, while the precision of PETCO 2 as a surrogate for PaCO 2 was independent of the PaCO 2 , PaO 2 , and SaO 2 as well as the extent of lung disease. Therefore, the end-inspiratory rebreathing technique may allow precise, noninvasive monitoring of PaCO 2 in ventilated patients, but further studies are required to identify the limitations of the method.