What is the least likely cause of hypoxemia to improve with increased FiO2?

The least likely cause of hypoxemia to improve with increased fraction of inspired oxygen (FiO2) is the presence of a shunt. In cases of a shunt, blood bypasses the alveoli where gas exchange occurs, meaning that even if the oxygen concentration in the inhaled air is increased, it does not effectively mix with the blood that is flowing through these shunted vessels. This results in continued low oxygen levels in the blood despite a higher FiO2 because the non-ventilated areas of the lungs cannot correct the oxygen deficit.

In contrast, hypoventilation and impaired diffusion may see some improvement in oxygen levels with increased FiO2. Hypoventilation leads to decreased overall ventilation but increasing FiO2 can help elevate arterial oxygen levels as it maximizes the oxygen available for exchange in whatever functioning alveoli are present. Similarly, impaired diffusion prevents adequate transfer of oxygen from the alveoli to the blood, but providing more oxygen can help force some diffusion to still occur.

Ventilation-perfusion (V/Q) mismatch is another condition that can improve with increased FiO2 as it suggests that while ventilation is not matching perfusion well, there are still ventilated areas that can benefit from the additional oxygen.

Thus